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Circadian patterns of urinary electrolyte excretion were investigated in normal subjects, and in conscious patients with (1) hypothalamic disease (without significant endocrinopathy), (2) extrahypothalamic central nervous system disease, and (3) pituitary disease. Normal patterns were observed in all cases of extrahypothalamic central nervous system disease. Abnormal patterns (consisting of phase reversal), were found in five of ten patients with hypothalamic disease. The patients with pituitary disease all tended to show flattening of the circadian pattern of urinary electrolyte excretion. The alteration observed in this group was independent of the extent of endocrinopathy present. These findings support the concept of a central nervous system role in the regulation of circadian patterns of urinary electrolyte excretion.

Laboratory evidence for hypogonadism has been sought in 33 patients with acromegaly and pituitary disease. Low serum testosterone was found in 7 of the 15 males with acromegaly and 4 of 4 with chromophobe adenomas. Clomiphene administration caused no rise in testosterone in the acromegalic tested; a normal response to HCG, however, was determined in another. Disparity between testosterone levels and sperm count in three subjects suggests that dissociation of follicle stimulating hormone (FSH) secretion from interstitial cell stimulating hormone (LH) secretion may occur in association with hypothalamic-pituitary disease. This study indicates that gonadotrophic insufficiency is a commonly associated feature of acromegaly in the male. Testosterone levels were depressed in four of the five females with hypoadrenalism and/or hypogonadism secondary to pituitary disease who were not on oestrogen substitution therapy.

Difficulties in airway management are observed among patients with pituitary disease. The purpose of this study was to better characterize the relationship between disease factors such as tumor characteristics on difficult endotracheal intubation. The perioperative records of 746 patients that underwent transsphenoidal microsurgery at the University of Virginia between January 1995 and June 2001 were reviewed. Among the 746 patients studied, difficulty with endotracheal intubation was encountered in 28 patients (3.8%). Patient gender and tumor size were not associated with a difference in the incidence of unanticipated airway management difficulty. Unanticipated difficulty with airway management was more than three times more common in acromegalic patients (n = 121) than in patients with nonfunctioning pituitary tumors (9.1% [5.8-14%] vs 2.6% [1.5-4.5%], P = 0.007). Patients with Cushing disease (n = 182) and patients with a prolactinoma (n = 87) were no more difficult to intubate than patients with nonfunctioning tumors. Among patients with acromegaly, neither tumor size nor patient gender has any impact on the incidence of intubation difficulty. Among all patients, when difficulty was encountered, intubation assisted by the gum elastic bougie was successful 100% of the time. The incidence of difficulty in intubation is not higher among patients with pituitary disease than in the general surgical population; however, patients with acromegaly have difficult intubations three times more often.

OBJECTIVE: The insulin-tolerance test (ITT) is currently considered to be the gold standard for evaluating adults suspected of GH deficiency (GHD). The aim of this study was to determine factors that may influence nadir blood glucose (BG) when using a mean insulin dose of 0.1 IU/kg body weight. Furthermore, we wanted to evaluate the safety and GH-related aspects of the ITT. DESIGN: ITT was performed in 277 patients, of whom 255 (129 females) were eligible for evaluation. RESULTS: Multiple regression analysis, including the whole population, showed that the major determining factors for nadir BG were basal BG and body mass index (BMI) (P

Hussain MA, Schmitz O, Jorgensen JOL, Christiansen JS, Weeke J, Schmid C, Froesch ER. Insulin-like growth factor I alters peripheral thyroid hormone metabolism in humans. Eur J Endocrinol 1996;134:563–7. ISSN 0804–4643 Insulin-like growth factor I (IGF-I) is considered to mediate some of the growth-promoting and metabolic effects of growth hormone (GH). Growth hormone treatment of healthy and GH-deficient subjects is accompanied by increased conversion of thyroxine (T4) to triiodothyronine (T3) in peripheral tissues. Whether these effects are mediated by IGF-I is unknown. To assess the respective roles of these hormones on thyroid hormone metabolism we have treated two groups of subjects. The first group consisted of eight healthy subjects who were treated with IGF-I 10 μg·kg−1·h−1 sc for 5 days). The second group consisted of eight subjects with combined GH and thyrotropin (TSH) deficiency due to acquired pituitary disease. They were treated with IGF-I (10 μg·kg−1·h−1 sc for 7 days), GH (2 IU m−2 sc q.i.d.) or both hormones together. The IGF-I treatment in healthy subjects led to an increase in free T3 (FT3) and a reduction in TSH levels, whereas FT4 and total T4 (TT4) levels remained unchanged. In the second group—in which all subjects were substituted with oral lthyroxine—treatment with IGF-I led to an elevation of FT3 in the face of unchanged T4 levels. Growth hormone alone and GH plus IGF-I resulted in a more pronounced elevation in T3 level. The results suggest that IGF-I partially mediates the well-known effects of GH on peripheral conversion of T4 to T3. However, GH has more pronounced effects on thyroid hormones that apparently are not mediated by IGF-I. ER Froesch, Division of Endocrinology and Metabolism, Department of Internal Medicine, University Hospital of Zürich, Rámistr, 100, 8091 Zürich, Switzerland

Patients treated for pituitary adenomas generally report a reduced quality of life (QoL). At present, the patient’s perspective of QoL has not been fully addressed and this, and further insight in potential determinants of QoL in pituitary diseases is required to design strategies to improve QoL. We aimed to define patients’ perceived QoL and to identify potential factors they perceive to contribute to QoL. We conducted four independent focus groups of six patients each, per specific pituitary disease (Cushing’s disease, Non-functioning pituitary macroadenoma, acromegaly, prolactinoma). In two sessions these focus groups discussed aspects of QoL. Verbatim transcripts were analyzed using a grounded theory approach. The issues raised by the patient groups were compatible with statements and items of available QoL questionnaires. In addition, other QoL aspects emerged, such as visual limitations (physical problems); issues with a desire to have children/family planning, fear of collapsing, fear of recurrence, panic, persisting thoughts, problems with an altered personality, anger, jealousy, sadness, frustration (psychological problems); and difficulties communicating about the disease, lack of sympathy and understanding by others, and a reduced social network (social problems). Next, this study uncovered factors which might contribute to a decreased QoL (e.g. less effective coping strategies, negative illness perceptions, negative beliefs about medicines, unmet needs regarding care). This focus group study demonstrated that important disease-specific aspects of QoL are neglected in current pituitary disease-specific questionnaires and elucidated potential factors that contribute to a decreased QoL. Information provided in this study can (and will) be used for developing additional items for disease-specific QoL questionnaires and for the development of a self-management intervention aiming to improve QoL in patients treated for pituitary diseases.

OBJECTIVE: To evaluate if fracture risk was increased in patients with Cushing's syndrome due to the increased endogenous cortisol production. DESIGN: Cohort. METHODS: A self-administered questionnaire was mailed to 125 patients with Cushing's syndrome diagnosed between 1985 and 1999 in Denmark. The response of each patient was compared with that of three age- and gender-matched control subjects randomly drawn among respondents to the same questionnaire from the background population. RESULTS: One hundred and four patients (83%) responded. The median age of the patients was 48 years (range 19-85 years). Sixty-eight had pituitary disease, 28 had adrenal disease, four had had both pituitary and adrenal surgery while four had not undergone surgery at the time of the study. The median time from diagnosis to surgery was 0.2 (range 0-3) years. Eighty-six percent were cured following surgery. There was an increased fracture risk within the last 2 years prior to diagnosis (incidence rate ratio 6.0, 95% confidence intervals (CI): 2.1-17.2). More than 2 years prior to diagnosis and following diagnosis there was no difference in fracture risk between patients and controls. The patients had more low-energy fractures than the controls (relative risk 5.4, 95% CI: 1.4-20.1). There was no difference in fracture risk between patients with adrenal or pituitary disease. CONCLUSIONS: Patients with Cushing's syndrome had an increased fracture risk in a narrow time interval before diagnosis, while no increase in fracture risk could be demonstrated after diagnosis and treatment.

Summary A young woman carrying germline DICER1 mutation was discovered to have a pituitary microprolactinoma when she became amenorrhoic. The mutation was identified as a result of family screening following the early death of the patient’s daughter with ovarian cancer. The patient was in follow-up screening for thyroid disease, and investigations were initiated when she became amenorrhoic. MR scan revealed a 6 mm diameter pituitary microadenoma and raised prolactin. The prolactin was efficiently suppressed with low-dose cabergoline, and her menstrual cycles resumed. Dicer is an RNase enzyme, which is essential for processing small non-coding RNAs. These molecules play pleiotropic roles in regulating gene expression, by targeting mRNA sequences for degradation. DICER1 plays different roles depending on cell context, but is thought to be a functional tumour suppressor gene. Accordingly, germline mutation in one DICER1 allele is insufficient for oncogenesis, and a second hit on the other allele is required, as a result of postnatal somatic mutation. Loss of DICER1 is linked to multiple tumours, with prominent endocrine representation. Multinodular goitre is frequent, with increased risk of differentiated thyroid cancer. Rare, developmental pituitary tumours are reported, including pituitary blastoma, but not reports of functional pituitary adenomas. As DICER1 mutations are rare, case reports are the only means to identify new manifestations and to inform appropriate screening protocols. Learning points: DICER1 mutations lead to endocrine tumours. DICER1 is required for small non-coding RNA expression. DICER1 carriage and microprolactinoma are both rare, but here are reported in the same individual, suggesting association. Endocrine follow-up of patients carrying DICER1 mutations should consider pituitary disease.

Purpose To review the clinical and biochemical characteristics and clinical outcome of patients presenting with pituitary apoplexy to a tertiary centre. Methods We retrospectively reviewed the clinical features, predisposing factors, biochemistry and clinical outcome of patients presenting with pituitary apoplexy to Imperial College Healthcare NHS Trust between 1991 and 2015. Results We identified 64 patients with pituitary apoplexy (more complete clinical records were available in 52 patients). The median age at presentation was 46.7 years (IQR 31.5–57.0 years). Pituitary apoplexy was the first presentation of pituitary disease in 38/52 of patients and predisposing factors were identified in 28/52. Pituitary apoplexy predominantly occurred in patients with non-functioning pituitary adenomas (47/52). Headache was most commonly described as sudden onset, severe, lateralising to the frontal or temporal regions. Symptoms of meningeal irritation were reported in 7/18 and visual abnormalities in 22/35. A pre-treatment serum cortisol Conclusions In conclusion, these data describe the clinical features of pituitary apoplexy to aid the clinician in diagnosing this rare emergency presentation of pituitary disease. Prospective multicentre studies of the presentation of pituitary apoplexy are required to further characterise presentation and outcomes.

The homeobox gene Hesx1/HESX1 has been implicated in the establishment of anterior pattern in the central nervous system (CNS) in a number of vertebrate species. Its role in pituitary development has been documented through loss-of-function studies in the mouse. A homozygous missense point mutation resulting in a single amino acid substitution, Arg160Cys (R160C), is associated with a heritable form of the human condition of septo-optic dysplasia (SOD). We have examined the phenotype of affected members in this pedigree in more detail and demonstrate for the first time a genetic basis for midline defects associated with an undescended or ectopic posterior pituitary. A similar structural pituitary abnormality was observed in a second patient heterozygous for another mutation in HESX1, Ser170Leu (S170L). Association of S170L with a pituitary phenotype may be a direct consequence of the HESX1 mutation since S170L is also associated with a dominant familial form of pituitary disease. However, a third mutation in HESX1, Asn125Ser (N125S), occurs at a high frequency in the Afro-Caribbean population and may therefore reflect a population-specific polymorphism. To investigate the molecular basis for these clinical phenotypes, we have examined the impact of these mutations on the regulatory functions of HESX1. We show that Hesx1 is a promoter-specific transcriptional repressor with a minimal 36 amino acid repression domain which can mediate promoter-specific repression by suppressing the activity of homeodomain-containing activator proteins. Mutations in HESX1 associated with pituitary disease appear to modulate the DNA-binding affinity of HESX1 rather than its transcriptional activity. Wild-type HESX1 binds a dimeric homeodomain site with high affinity (Kd 31 nM) whilst HESX1(S170L) binds with a 5-fold lower activity (Kd 150 nM) and HESX1(R160C) does not bind at all. Although HESX1(R160C) has only been shown to be associated with the SOD phenotype in children homozygous for the mutation, HESX1(R160C) can inhibit DNA binding by wild-type HESX1 both in vitro and in vivo in cell culture. This dominant negative activity of HESX1(R160C) is mediated by the Hesx1 repression domain, supporting the idea that the repression domain is implicated in interactions between homeodomain proteins. Our data suggest a possible molecular paradigm for the dominant inheritance observed in some pituitary disorders.

Summary As growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) levels decrease with age, it isimportant to have reliable age- and sex-specific control data for both GH stimulation tests and circulating IGF-I levels. This is particularly true for elderly patients with a history of pituitary disease but with normal production of the anterior pituitary hormones other than GH. The potential impact of these factors on GH deficiency (GHD) has led to a need for the development of reliable, sensitive and specific tests to assess GH reserve. Before starting treatment with recombinant human GH in adults with suspected GHD, it is important to differentiate between adults with childhood onset GHD (CO-GHD) and those with adult onset GHD (AO-GHD). Adults with untreated CO-GHD have significantly lower values for body weight, body mass index, lean body mass and height than those with AO-GHD, while patients with AO-GHD show a more pronounced deviation from normal in psychosocial distress. Following treatment with GH, 12.5 μg/kg/day s.c., patients with AO-GHD showed a decrease in waist/hip ratio and low-density lipoprotein. Quality of life, as measured using the Nottingham Health Profile, changed significantly in both patient groups after 18 months of therapy, though these results were only consistent in subjects with AO-GHD. Improvements were also reported in physical mobility and energy. Side-effects were mainly reported in patients with AO-GHD, and this may have been due to the GH dosage being too high for older patients. In conclusion, CO-GHD in adults appears to be a developmental disorder in patients who have not attained full somatic maturation. The hormonal/metabolic balance and lifestyle of these individuals have adapted to their condition. AO-GHD is a metabolic disorder characterized by a hormonal imbalance affecting the health status, physical condition and quality of life of previously normal adults.

Summary Hypothalamic-pituitary disease is a well-recognized, although uncommon, occurrence in sarcoidosis. Almost always the endocrine manifestations occur in a patient with widespread disease involving the lungs, skin or liver. A case is reported of central nervous system (CNS) sarcoidosis with no other clinical, biochemical or histological evidence of the disease.

The patient with Nelson's syndrome in this report represents an unusual case in which regular cyclic menstruation was preserved even though a large ACTH-producing pituitary adenoma was present. Despite normal menses and pregnancy, the radiologic findings of an enlarged sella turcica and an enhanced lesion on CAT scan were identified. This case demonstrates that patients with normal menstruation can have significant pituitary disease, and it exemplifies the need for regular follow-up examination to look for radiologic abnormalities in patients who have had adrenalectomy for treatment of Cushing's disease.

• Cerebrospinal fluid polyamine determinations were performed in 21 patients harboring pituitary tumors and six patients with nonneoplastic pituitary disease. Although CSF putrescine levels were significantly elevated in some patients harboring tumors, other patients showed no elevation. Polyamine levels did not correlate with tumor size, as assessed by the presence or absence of suprasellar extension. Data on patients harboring nonneoplastic pituitary disease were variable. Compared with other findings from this laboratory on the use of polyamine levels for the diagnosis and management of other brain tumors, these findings suggest that CSF polyamine levels will not have a significant diagnostic role in the treatment of patients suspected to have pituitary disease.

Head and neck symptoms occurred in 87% of patients (14 of 16) with eosinophilic granuloma seen in a 5 year period. Two patients with head and neck disease died (14% mortality). Both had concomitant pituitary disease. The underlying pathology was discovered in each instance only after a year of extensive diagnostic effort. The specific problems in diagnosis and treatment are apparent in the case report of an initially misdiagnosed patient. The following recommendations are suggested to optimize the care of such patients. Eosinophilic granuloma must be suspected in a variety of clinical settings. Radiography is the only helpful noninvasive study and definitive diagnosis depends on microscopic tissue examination. Patients with symptoms of pituitary disease pose a frustrating diagnostic problem because of the inaccessibility of the location for pathologic study. In contrast, the head and neck, ear, nose and throat are easily biopsied and comprise the region most frequently involved. A careful examination of this area is mandatory in all patients with symptoms consistent with eosinophilic granuloma intracranially or elsewhere if the disease is to be diagnosed and treated without delay.

The unusually high sensitivity and specificity of the serum free thyroxine (FT 4 ) index—the product of the total thyroxine (T 4 ) and triiodothyronine (T 3 ) uptake—makes this readily obtainable laboratory measurement a superb discriminator of thyroid dysfunction, even where the clinical findings of hypothyroidism or thyrotoxicosis are minimal or lacking. In thyrotoxicosis, elevation of the FT 4 index is an almost universal finding, occurring even before symptoms and signs are evident. In the unusual case of T 3 thyrotoxicosis (T 3 toxicosis), the FT 4 index may not reflect the thyrotoxic state, but determination of the T 3 concentration and calculation of the free T 3 FT 3 index enable the diagnosis to be made readily. The T 3 concentration and FT 3 index are not good tests for hypothyroidism, since the results are normal in 30% to 50% of proved cases; but in the absence of pituitary disease, elevation of the thyroid-stimulating hormone (TSH) will presage the disorder

Human growth hormone (HGH) secretion was assessed in 47 consecutive patients with pituitary disease and was compared to the secretion of other pituitary hormones. Nine patients had acromegaly and HGH hypersecretion, two had adrenocorticotropic hormone hypersecretion and Cushing syndrome, and two had nonpuerperal galactorrhea (prolactin hypersecretion). Twenty-nine patients had HGH deficiency, 21 had follicle-stimulating hormone—luteinizing hormone deficiency, 15 had thyroid-stimulating hormone deficiency, and 10 had adrenocorticotropic hormone deficiency. Abnormal HGH secretion appears to be the most frequent endocrine dysfunction among patients with pituitary disease.

We report a 10 year old female with Cushing's disease with recurrent disease 5 yrs after successful pituitary irradiation. At presentation, bone age, skull films, head CT and visual fields were all normal. Basal serum F, urinary 17-OHCS, free cortisol (F), and 6β-hydrocortisol (6β-OHF) were elevated. Serum F lacked circadian variation and was partially suppressed by high dose dexamethasone (dex). She received pituitary irradiation with a cumulative dose of 4,000 rads over a 1 month period. Serum F, 17-OHCS, 6β-OHF, urinary free F returned to normal, growth velocity improved, and puberty ensued with menarche occurring 3 yrs after irradiation. However, lack of diurnal variation of F persisted. Despite radiotherapy, five years later she developed clinical and biochemical evidence of mild recurrent Cushing's disease. Bone age, head CT, visual fields, and TRH, LHRH and L-DOPA/glucagon testing were all normal. Morning cortisol, 17-OHCS, and 6β-OHF were elevated and were partially suppressed only after high dose dex. The 8:00 PM ACTH level was elevated to 40 pcg/ml. After ovine CRF administration the maximum ACTH response was 46 pcg/ml; the ACTH concentration is increased and the absent ACTH response to CRF is abnormal. In patients with Cushing's disease treated with radiotherapy, the ACTH response to CRF stimulation may not be reliably compared to that of normal controls. Conclusion: Therefore Cushing's disease may recur despite successful pituitary irradiation. This suggests a hypothalamic CRF producing lesion as the primary lesion in Cushing s disease.

Recent advances in neurosurgical techniques have made it possible to remove pituitary adenomata with minimal morbidity and mortality. These developments have focused attention on early recognition of pituitary tumors, before the onset of visual disturbances or endocrine dysfunction. We have studied the prolactin response to insulin-induced hypoglycemia as an aid in the evaluation of patients with hypothalamic and pituitary disease. Regular insulin 0.1 units/kg was administered intravenously to normal subjects, to patients with pituitary tumors, and to patients with idiopathic galactorrhea. While the normal subjects regularly showed a prolactin response to hypoglycemia, this was observed infrequently in the other groups. It is possible that prolactin nonresponsiveness to insulin hypoglycemia may reflect nonspecific pituitary damage or may represent an abnormality specific to patients with galactorrhea. Our data suggest that the prolactin response to insulin hypoglycemia is a sensitive index of hypothalamic-pituitary dysfunction.

Excerpt Man's infirmities are as old as man himself; and in some instances the infirmity existed as a potential pathologic state before man's advent on this earth, awaiting his arrival to fasten it...

The first operation in the neurosurgical clinic of the University Hospital for the relief of a symptom or effect of primary pituitary disease was performed in 1912, and since that time 175 patients have been added to our pituitary register. While surgery is recognized as a factor in the care of the patient with pituitary disorder, yet there is a certain amount of hesitation or uncertainty on the part of physicians as to what advice to give such patients. It is only proper that a fair statement should be made as to what may be accomplished by such methods of treatment as are available; to wit, glandular therapy, radiotherapy and operation. TREATMENT I can pass over the merits of glandular therapy, as my experience has been entirely barren of results and this applies only to patients who have already developed pressure symptoms. Obviously, such patients as may have responded to

Findings in eight patients with acanthosis nigricans and pituitary tumors, seven of whom had acromegaly or gigantism, emphasize the association of this dermatosis with pituitary disease. The sex incidence was equal, and their ages varied between 15 and 46 years. Two male patients had diabetes mellitus; three of four female patients had hypertrichosis, and all four female patients had amenorrhea. Obesity was not a constant feature. The clinical and histological findings were similar to those in acanthosis nigricans associated with other diseases. The occurrence of acanthosis nigricans with pituitary tumors as well as with other endocrine diseases, drugs, and total lipodystrophy raises the question of a possible hormonal or metabolic relationship of this dermadrome.

Within the last few years there have appeared several reports 1 to the effect that the specific dynamic action of food is decreased in so-called pituitary disease. No studies of this question appear to have been made on laboratory animals, though there are reports of lowered basal metabolism following surgical removal of or injury to the hypophysis (Benedict and Homans 2 in the dog, Winton and Hogben 3 in the frog). However, much of the work of these investigators is inconclusive on account of the ill defined nature of their experimental material as seen in the light of recent investigations of hypophysial function. The experimental work of Camus and Roussy, 4 Bailey and Bremer 5 and Smith, 6 and the clinical cases of pituitary atrophy, reported by M. Simmonds 7 and others show that a pituitary deficiency does not give rise to obesity. Since most of the clinical cases, aside

In the extensive literature on the specific dynamic action of food there have appeared a number of articles relating to the effect of the endocrine glands on this feature of metabolic activity. Experimental studies have led to varied conclusions as to the role played by the glands of internal secretion in altering the specific dynamic response to food. Foreign investigators in particular have reported finding this response diminished or completely absent in patients with diseases of the thyroid or pituitary gland. 1 In this country Baumann and Hunt, 2 Foster and Smith 3 and others have noted an abnormal specific dynamic response immediately following the administration of dextrose or amino-acids in rabbits and rats deprived of their thyroid or pituitary glands. Some of the workers, notably Kestner, Liebeschutz-Plaut and Schadow, 4 and Foster and Smith, 3 have reported an increase in the specific dynamic action when preparations of pituitary gland

According to the figures given by various authors, diabetes occurs in from 10 to 40 per cent of the cases of acromegaly. Even the lowest of these figures is sufficiently high to suggest that this is more than a coincidence, that there must be some common factor underlying both conditions. In going over the older literature one finds that most of the diagnoses of diabetes in these cases have been made on the basis of the urinary examinations for sugar. In considering this subject, therefore, we must bear this point in mind for in the light of more recent work we know that glycosuria is not always a true indication of diabetes. In an analysis of all cases of pituitary disease which have been seen at the Cleveland Clinic, comprising forty-one cases to date, seven cases of acromegaly were found, diabetes being present in two of these, 28.5 per cent.

The attention of an observer is attracted to diseases of the endocrine system by unmistakable abnormality of development in young individuals, by a group of signs of variable definiteness or by autopsy observations. Except in certain gigantic states and sexual dystrophies, changes in anatomy and physiology of the pituitary body do not express themselves in a clear-cut manner. Acromegalic and genital alterations, while fairly clear in the human being, are not by any means so readily determined in the lower animals. This is especially true of wild varieties. In a reasonably complete review of the literature I did not discover a satisfactory case of pituitary disease in wild animals. There are numerous references in the literature to inflammation, strumas and tumors in the domestic animals, and there is a considerable volume of writing about the state of the hypophysis during pregnancy and hibernation. However, the relationship of pathologic to clinical

Tumors of the pituitary body are usually recognized by either or both of two general symptoms: those directly due to pressure of the growth on adjacent structures and those due to glandular dysfunction. The commonest pressure phenomena observed are encroachment on the optic chiasm producing visual field cuts, and deformity of the sella turcica from increased tension within. The changes of glandular origin may be due to a disturbance of the anterior or posterior lobes of the pituitary body, of adjoining tissues, or of distant glands of internal secretion. The functions of these various organs and their interrelationship are not definitely established and this fact makes the interpretation of some of the symptoms of primary pituitary disease difficult. Some rather conclusive experimental work has been done on the functions of the anterior lobe of the pituitary body. For the purpose of this analysis fifty cases of primary pituitary tumors were

To the Editor: —InThe Journal, January 2, page 31, Dr. Sigurd W. Johnsen reports a case of pituitary disease in a boy, aged 4. This is apparently not a case of pituitary disease, but a classical example of "pubertas praecox," a condition associated most commonly with pinealomas, as discussed in a recent paper by Horrax and Bailey ( Arch. Neurol. & Psychiat. 13:423 [April] 1925). The literature on the pituitary body is already overburdened with a mass of conflicting opinions and theories of clinicians, experimental physiologists and pathologists. In the case referred to the only evidence of pituitary disease is a roentgenogram of an enlarged sella. This may be produced by a cerebral tumor or internal hydrocephalus, as well as a pituitary neoplasm. [The letter of Dr. Fink was referred to Dr. Johnsen, who replies:]

The ductless glands with their important influence on the growth, development and maintenance of the body, physical and mental, occupy a notable position in the realm of medicine today, yet a few generations ago they were wholly neglected and almost unknown. About the middle of the last century Claude Bernard, Brown-Sequard and others popularized their use in therapy; but the suggestions offered by them were not followed up, and the value of the work then accomplished was largely forgotten. Langley and Gaskell in England, Beedl in Vienna, and Bouchard in France have in recent years vastly increased our knowledge of the action of these glands. On the facts these observers have discovered, a complete system of therapy has been erected and generalizations regarding their influence in disease have been recklessly enunciated as dogmas. Coincidence became confused with causation. As clinicians add to our store of facts, the skepticism of the

Excerpt The history of the relation of a disturbance in sugar metabolism to pituitary disease may be divided into two epochs, that prior to 1911, when rough, more or less scientific observations sh...

Several hundred obese children have been referred to us as having Frohlich's syndrome, or dystrophia adiposogenitalis. These patients were presumed to have pituitary disease or a combination of pituitary with thyroid involvement. Approximately 80 of this number1have been studied thoroughly from the point of view of physical development (sexual and mensurational) (fundi and visual fields), and complete laboratory studies were made, including roentgenographic examination of the head (sella turcica), wrist and knee, and basal metabolism, blood cholesterol and sugar tolerance tests. In addition, we have used a roentgenographic cephalometric appraisal2to study the problem further. Analysis of the craniofacial system by this method showed that in general the skeletal development in an unselected group of some 20 obese boys and girls was normal and even in advance of that in normal controls. We have also made cephalometric studies of thyroid-deficient3and dwarfish4(pituitary) children and so

To the Editor: —It is true that the literature on the pituitary body is a mass of conflicting opinions and theories. The same is true, however, for many of the other ductless glands. Who will set himself up as the authority to decide what clinical symptoms or syndromes are characteristically associated with pathologic changes in the pituitary body, in early as well as the later stages? Cushing has reported cases which clinically simulate the case which I reported as being due to hypersecretion of the suprarenal bodies. Bailey has reported somewhat similar cases as being due to hypersecretion of the pineal body. Barker has described such cases as being due to hypersecretion of the pituitary body. Edward B. Towne, in speaking of ossification changes before the epiphyseal cartilages are ossified, says: "If ossification is incomplete there is excessive skeletal growth resulting in fairly normally proportioned gigantism primarily of pituitary origin."

The following case is reported in the hope of helping to solve the riddle of the symptom complex of disease of the kidneys and bones, dwarfing and infantilism, which goes by the name of renal rickets and dwarfism. REPORT OF A CASE Dorothy H. (fig. 1), aged 18½ years, the second child of healthy parents, was born at term weighing 8 pounds (3,629 Gm.). She was nursed for three months. After weaning, no difficulty was experienced with her feeding. She took solid food as readily as her brother had. She walked and talked at the age of 2 years. The parents were not blood relatives. There was no known dwarf, giant or exceedingly thin person among the relatives. The maternal grandmother weighed about 200 pounds (90.7 Kg.). The maternal grandfather had died at the age of 42 of heart trouble. First Admission.—The girl was admitted first on April 21

R. B. was admitted to the surgical ward after an automobile accident, suffering from minor abrasions of the face, and a slight scalp laceration. He appeared to be about 10 years of age; he was well developed, but had an unusually well developed penis, like that of an adult, and an abundance of pubic hair. On the arrival of his father, it was ascertained that the boy was 4 years of age. He was born, April 15, 1921, of normal delivery, at home, and weighed 9½ pounds (4.3 kg.). At the age of 1 month, the mother noticed that the bowels were habitually constipated. She then gave him daily cathartics. He was breast fed until 4 months old. After that he was given 4 ounces (120 c.c.) of whole milk every three or four hours. At the age of 14 months he had an attack of convulsions, followed by two