Search

Different etiologies of hypopituitarism may give rise to distinct patterns of hormone deficiency, all causes may eventually lead to panhypopituitarism. Typically, pituitary tumors lead to gradual loss of anterior pituitary hormones with disinhibition of prolactin release. Progressive pituitary failure related to tumor or irradiation results in growth hormone (GH) deficiency, followed by sequential loss of the other hormones of the anterior pituitary: luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), and finally adrenocorticotropin hormone (ACTH). Loss of posterior pituitary function resulting in diabetes insipidus rarely occurs as a direct result of a pituitary mass lesion, with pituitary metastasis being an important exception. Deficiency of antidiuretic hormone (ADH) commonly occurs in hypothalamic lesions, and transient or permanent ADH deficiency may complicate trauma to the pituitary fossa, as seen in surgery and pituitary apoplexy. This chapter discusses the etiologies of hypopituitarism and the optimal approach to hormone replacement therapy for ACTH, TSH, LH/FSH, GH and ADH deficiency.

In many countries, treatment of childhood-onset GH deficiency (GHD) with GH ceases when linear growth is complete. Peak bone mass occurs several years after the completion of linear growth. Given that GH has important anabolic actions on bone, discontinuation of GH therapy at the completion of linear growth may have adverse consequences for the attainment of peak bone mass in adolescent GHD patients. In this United Kingdom multicenter study, 24 adolescents (13 males, mean age 17.0 +/- 1.4 yr, SD) with severe GHD were randomized to discontinue or continue GH (0.35 IU/kg x wk) at the completion of linear growth. Whole body bone mineral content (BMC) and lumbar spine bone mineral density were assessed by dual-energy x-ray absorptiometry at baseline and then at 6-month intervals for 1 yr. Markers of bone remodeling (serum bone-specific alkaline phosphatase and urinary deoxypyridinoline) were measured at the same time points. In patients who continued GH (GH+), median BMC increased by 3.8% (interquartile range, 2.6, 5.9, P < 0.001) at 6 months; and by 6.0% (3.7-9.1, P < 0.001) at 12 months. In patients who discontinued GH (GH-) median BMC was unchanged at 6 and 12 months (+1.9%, -0.4-4.2, P = 0.9; and +2.4%, 0.4-4.9, P = 0.5, respectively, median, interquartile range). The differences in median change in BMC between the two groups at 6 and 12 months was marginally significant (P = 0.085 and 0.074, respectively). Mean lumbar spine bone mineral density increased by 4.7 (95% confidence interval, 1.0, 8.2) at 12 months in patients continuing GH (P = 0.01), but the mean change was not statistically significant change in patients who discontinued GH [+2.7% (95% confidence interval, -0.8, +6.2)]. These preliminary data suggest that, in adolescent patients with severe GHD, discontinuation of GH at completion of growth may limit the attainment of peak bone mass in this patient group. This may predispose to clinically significant osteopenia in later adult life.

Type 1 diabetes is associated with abnormalities of the growth hormone (GH)-IGF-I axis. Such abnormalities include decreased circulating levels of IGF-I. We studied the effects of IGF-I therapy (40 microg x kg(-1) x day(-1)) on protein and glucose metabolism in adults with type 1 diabetes in a randomized placebo-controlled trial. A total of 12 subjects participated, and each subject was studied at baseline and after 7 days of treatment, both in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp. Protein and glucose metabolism were assessed using infusions of [1-13C]leucine and [6-6-2H2]glucose. IGF-I administration resulted in a 51% rise in circulating IGF-I levels (P < 0.005) and a 56% decrease in the mean overnight GH concentration (P < 0.05). After IGF-I treatment, a decrease in the overnight insulin requirement (0.26+/-0.07 vs. 0.17+/-0.06 U/kg, P < 0.05) and an increase in the glucose infusion requirement were observed during the hyperinsulinemic clamp (approximately 67%, P < 0.05). Basal glucose kinetics were unchanged, but an increase in insulin-stimulated peripheral glucose disposal was observed after IGF-I therapy (37+/-6 vs. 52+/-10 micromol x kg(-1) x min(-1), P < 0.05). IGF-I administration increased the basal metabolic clearance rate for leucine (approximately 28%, P < 0.05) and resulted in a net increase in leucine balance, both in the basal state and during the hyperinsulinemic amino acid clamp (-0.17+/-0.03 vs. -0.10+/-0.02, P < 0.01, and 0.25+/-0.08 vs. 0.40+/-0.06, P < 0.05, respectively). No changes in these variables were recorded in the subjects after administration of placebo. These findings demonstrated that IGF-I replacement resulted in significant alterations in glucose and protein metabolism in the basal and insulin-stimulated states. These effects were associated with increased insulin sensitivity, and they underline the major role of IGF-I in protein and glucose metabolism in type 1 diabetes.

We report two cases of severe cardiac tamponade following cardiac surgery. In each case a haemorrhagic collection resulted in a localised tamponade. The clinical presentation in both cases was atypical and, although the possibility of tamponade was considered, the absence of classical signs delayed diagnosis until echocardiography was performed. These cases illustrate the varied presentation of tamponade after cardiac surgery which may be localised, highlighting the need for a high level of clinical suspicion and early use of echocardiography to make a prompt diagnosis. The transoesophageal echocardiogram may have particular relevance in the detection of localised collections causing a tamponade effect. The cases indicate that post-operative cardiac tamponade occurs over a wide time-scale following surgery and that anticoagulation may be a contributing factor.

Hypopituitarism most commonly results from pituitary/peripituitary tumors and their treatment. In those hypopituitary patients without structural abnormalities, transcription factor abnormalities are now increasingly recognized as accounting for insidious pituitary failure that is often termed “idiopathic.” Loss of pituitary hormone secretion may be partial or complete, and although different etiologies may give rise to distinct patterns of hormone deficiency, all causes may eventually lead to panhypopituitarism. Typically, pituitary tumors lead to gradual loss of anterior pituitary hormones with disinhibition of prolactin release. Progressive pituitary failure related to tumor or irradiation results in growth hormone deficiency, followed by sequential loss of the other hormones of the anterior pituitary: luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, and finally adrenocorticotropin hormone. Loss of posterior pituitary function resulting in diabetes insipidus rarely occurs as a direct result of a pituitary mass lesion, with pituitary metastasis being an important exception. Deficiency of antidiuretic hormone (ADH) commonly occurs in hypothalamic lesions, and transient or permanent ADH deficiency is not uncommon following trauma to the pituitary fossa, as seen in surgery and pituitary apoplexy.