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Purpose: The diagnosis of primary hyperparathyroidism (PHPT) and chronic hypoparathyroidism (HypoPT) is still challenging, especially in patients asymptomatic or with non-classical phenotypes and for physicians not skilled in calcium-phosphorous (Ca–P) disorders. The serum calcium/phosphorous (Ca/P) ratio has been proposed as accurate index to identify PHPT, while it has never been tested in HypoPT. The aim of this study is to investigate the diagnostic power of the serum Ca/P ratio in the diagnosis of primary parathyroid dysfunctions (both PHPT and HypoPT) in a large series of data. Methods: A multicentric, retrospective, cross-sectional study (ClinicalTrials.gov: NCT03747029) was carried out including 432 PHPT patients and 217 HypoPT patients compared with 389 controls. Serum Ca, P, creatinine, parathyroid hormone and 25OH-vitamin D were collected. Serum Ca and P were expressed in mmol/L. Ca/P diagnostic performance was evaluated by receiver operating characteristic (ROC) curve, sensitivity, specificity and accuracy. Results: The Ca/P ratio was significantly higher in PHPT and lower in HypoPT patients than controls (p < 0.0001). At ROC curve analysis, the Ca/P ratio above 2.55 was defined to identify PHPT patients (sensitivity 85.7%, specificity 85.3%) and below 1.78 to identify HypoPT patients (sensitivity 88.2%, specificity 87.9%). Conclusions: The Ca/P ratio is a highly accurate index to identify PHPT when Ca/P is above 2.55 and HypoPT when it is below 1.78. These results demonstrate the reliability of this index to rule in/out primary parathyroid dysfunctions and remark the importance of measuring serum P in clinical practice.

Background: Double pituitary adenomas (DA) are two morphologically and immunohystochemically different tumours in the same gland. They are rare, generally small adenomas and divided in: separated, when clearly recognizable before or during surgery, and contiguous, when diagnosed only in the following histopathological examination. Acromegaly and Cushing’s disease are the main prevalent clinical presentation. Objective: We described two cases of DA in a surgical series over 16 years in a single center. Methods: In September 2018, we diagnosed a DA in a man with acromegaly (case 1). In order to assess the presence of other cases of DA, we performed a retrospective analysis of the endonasal endoscopically operated sellar adenomas from January 2004 to December 2019. Results : 468 pituitary adenomas were found. A DA with a Pit-1 positive macroadenoma (GH-TSH- PRL positive) and an ACTH microadenoma clinically silent in an acromegalic woman was retrospectively found (case 2). Conclusion : Our analysis confirms that DA are rare (0.4% of the pituitary adenomas) and often associated with acromegaly. Their pre-operatively diagnosis is difficult but clinician’s awareness of DA can improve the diagnosis. The use of pituitary transcription factors could be useful in detecting DA.

A 75-year-old man was hospitalized because of severe hypokalaemia due to ACTH dependent Cushing’s syndrome. Total body computed tomography (TBCT) and 68 Gallium DOTATATE PET/CT localized a voluminous prostate tumour. A subsequent transurethral prostate biopsy documented a small cell carcinoma positive for ACTH and calcitonin and negative for prostatic specific antigen (PSA) at immunocytochemical study; serum prostatic specific antigen (PSA) was normal. Despite medical treatments, Cushing’s syndrome was not controlled and the patient’s clinical condition progressively worsened. Surgical resection was excluded; the patient underwent a cycle of chemotherapy followed by febrile neutropenia and fatal intestinal perforation. This case report describes a rare case of Cushing’s syndrome and hypercalcitoninaemia due to a small cell carcinoma of the prostate, a rare tumour with very few therapeutic options and negative prognosis.

Strong evidence indicates that bone marrow cells (BMCs) can contribute to the healing process of injured vascular system via CXCR4/Thymosin beta4/Integrin alpha4beta1/SDF-1 molecular pathways. We discuss the therapeutic approaches of BMCs and circulating endothelial progenitor cells (EPCs) to restore vascularization. Today some clinical trials employing BMCs in the treatment of peripheral vascular diseases have been completed with encouraging results. When large clinical controlled studies will be completed, the scientific community will evaluate this novel and promising therapeutic approach. Although some basic studies suggest the potential use of adult/somatic stem cell for vascular repair, other stringent data suggest that this potential is dependent also on growth factor synthesis rather than the formation of new arterial vessels. Considering the limitations of adult stem cells especially in elderly subjects, our point of view is that BMCs or exogenous BMC/EPC are candidate for adjunct cell-therapy applications in vascular repair.

Introduction The prevalence of erectile dysfunction (ED) and its correlates in men with acromegaly has never been investigated. Aim The aim of this study was to evaluate sexual function in men with acromegaly. Methods Multicenter-based, retrospective analysis of a nonselected series of 57 acromegalic subjects (mean age: 52.7 ± 14.2 years) was performed. Acromegalic subjects reporting ED (n = 24) were compared with matched ED patients without acromegaly or pituitary disease (controls), selected from a cohort of more than 4,000 subjects enrolled in the Florence Sexual Medicine and Andrology Unit. Main Outcome Measures Patients were interviewed using Structured Interview on Erectile Dysfunction (SIEDY) structured interview, a 13-item tool for the assessment of ED-related morbidities. Several clinical and biochemical parameters were taken. Penile color Doppler ultrasound (PCDU) was performed in a subgroup of 37 acromegalic subjects. Results ED was reported by 42.1% of acromegalic subjects. After adjusting for age and testosterone, acromegalic subjects with ED had a higher prevalence of hypertension and more often reported an impairment of sleep-related erections and a longer smoking habit. Accordingly, acromegaly-associated ED was characterized by a higher organic component and worse PCDU parameters. No relationship between ED and testosterone levels or other acromegaly-related parameters was found. However, acromegalic subjects with severe ED reported a longer disease duration. In a case-control analysis, comparing acromegalic subjects with ED-matched controls free from acromegaly (1:5 ratio), acromegalic men had a worse ED problem and a higher organic component of ED, as derived from SIEDY score. In line with these data, acromegalic patients with ED had a higher prevalence of major adverse cardiovascular events history at enrollment and lower PCDU parameters. Conclusions Subjects with complicated acromegaly are at an increased risk of developing ED, especially those with cardiovascular morbidities. Our data suggest including a sexual function evaluation in routine acromegaly follow-up.

The reports of congenital estrogen deficiency - notably, estrogen resistance and aromatase deficiency - have completely changed our knowledge on the role of estrogen on bone in males. Particularly, the bone changes at puberty, which were classically considered androgen-dependent, are now considered to be induced at least in part by estrogen action. Clinical cases of congenital estrogen deficiency have clearly demonstrated that the role of estrogens in epiphyseal closure, skeletal proportions and bone mineralization is crucial not only in women but also in men. In addition progress have been made in the treatment of such a rare disease even though further studies are needed to a definitive understanding of this issue.

OBJECTIVE In order to evaluate the role of oestrogens on human male sexual behaviour, the gender-identity, psychosexual orientation and sexual activity of a man with a congenital lack of oestradiol resulting from an inactivating mutation of the aromatase P450 gene was investigated. The psychosexual and sexual behavioural evaluations were performed before and during testosterone treatment and before oestradiol treatment, during three phases of different dosages of oestradiol treatment. DESIGN The study was performed before (phase A) and during (phase B) testosterone enanthate treatment (250 mg i.m. every 10 days, for 6 months), during testosterone withdrawal (phase C), and during each of the following transdermal oestradiol treatments: 50 μg twice a week for 6 months (phase D); 25 μg twice a week for 9 months (phase E), and 12.5 μg twice a week for 9 months (phase F). MEASUREMENTS Sexual behaviour was investigated by a sexological interview and by a 2-month self-reported daily diary performed during each phase of the protocol study. Furthermore, during each oestradiol treatment (phase C, D, E and F), a study of depression, anxiety trait and sexual behaviour was performed by the Beck Depression Inventory (BDI), the Spielberger Trait Anxiety Inventory (STAI) and the Golombok-Rust Inventory of Sexual Satisfaction (GRISS), respectively. Sexual orientation and gender-identity were evaluated by the BEM Sex Role Inventory (BSRI). Serum testosterone and oestradiol were measured during each phase of the study. RESULTS Before oestradiol treatment (phase C), serum oestradiol was undetectable, while it rose to 356.1, 88.1 and 55.1 pmol/l during phases D, E and F, respectively. Before any oestradiol treatment, during phase D, phase E and phase F serum testosterone was 18.13, 0.72, 14.3 and 18.51 nmol/l, respectively. The patient's gender-identity as assessed by BSRI and by the sexological interview was clearly male. The psychosexual orientation evaluated by BSRI, by the sexological interview and by the analysis of the self-filled diary was heterosexual. Relevant modification of the patient's sexual behaviour occurred only during oestrogen treatment. This was more evident during both phase E and phase F, and concerned the behavioural parameters with an increase of libido, frequency of sexual intercourse, masturbation and erotic fantasies. A reduction of BDI and STAI scores was detected during the oestrogen phases. CONCLUSIONS The study of the sexual behaviour in this man with aromatase deficiency suggests that oestrogens in humans do not affect gender-identity and sexual orientation but could have a role in male sexual activity.

Cushing's syndrome may remain unrecognized among patients referred for metabolic syndrome; thus, a proactive screening has been suggested in certain patient populations with features of the disorder. However, conflicting data have been reported on the prevalence of Cushing's syndrome in patients with type 2 diabetes.Our aim was to evaluate the prevalence of unsuspected Cushing's syndrome among outpatients with type 2 diabetes.This was a cross-sectional prospective study in 24 diabetes clinics across Italy.Between June 2006 and April 2008, 813 patients with known type 2 diabetes without clinically overt hypercortisolism were evaluated. Follow-up of the study was closed in September 2010. Patients were not selected for characteristics conferring a higher pretest probability of hypercortisolism. Patients underwent a first screening step with the 1-mg overnight dexamethasone suppression test.Forty patients failed to suppress serum cortisol less than 5.0 μg/dl (138 nmol/liter) and underwent a standard 2-d, 2-mg dexamethasone suppression test, after which six patients (0.6% of the overall series) failed to suppress cortisol less than 1.8 μg/dl (50 nmol/liter), receiving a definitive diagnosis of Cushing's syndrome that was adrenal dependent in five patients. Four patients were cured, being able to discontinue, or reduce, the glucose-lowering agents.The present data do not support widespread screening of patients with type 2 diabetes for Cushing's syndrome; however, the disorder is less rare than previously thought when considering epidemiology of type 2 diabetes. Our results support a case-finding approach in patients with uncontrolled diabetes and hypertension despite appropriate treatment.

To study the effects of sildenafil on human sleep-related erections according to the state of androgenization, we evaluated the effects of sildenafil on sleep-related erections in hypogonadal men before and during testosterone replacement treatment and in control subjects. We enrolled 24 hypogonadal men and 24 healthy men as a control group. All hypogonadal subjects had very low testosterone levels (

Osteonecrosis of femoral head is related to different predisposing factors. The pathogenesis is not completely understood, but an ischemic impairment seems to be one of the major determinants of bone necrosis. The association of bilateral necrosis of femoral heads and congenital aromatase deficiency is here reported. The absence of estrogen activity, as well as the persistence of unfused epiphyses for a long period of life, may be involved in the determinism of bilateral necrosis of bone femoral heads. The possibility of development of bone necrosis in patients affected by congenital estrogen deficiency needs to be considered and magnetic resonance imaging can be a useful method for an early detection of this disease.

The report focuses on the role of estrogens in human male, dealing with two human models of congenital estrogen deficiency: estrogen resistance and aromatase deficiency. Similarities and differences of clinical phenotypes of these models are described and progresses of estrogen treatment of aromatase-deficient men are reported. Finally, the putative use of estrogen in men and the use of aromatase inhibitors and antiestrogen for male disorders are discussed.

Experimental data support a role for GH and IGF-I in the reproductive process in humans, but the effect of chronic GH excess on gonadal and reproductive function in men has been never investigated. To understand the effects of short-term GH and IGF-I suppression on the gonadal axis and seminal fluid characteristics in men with acromegaly, we evaluated 35 patients (age 27–59 yr) with active disease and 35 age-matched healthy controls. Gonadal hormones and seminal fluid analysis were evaluated before and 6 months after surgery or lanreotide (LAN) (60 mg/month). At study entry, FSH, testosterone (T), and dihydrotestosterone (DHT) (P < 0.0001) levels, seminal volume, sperm count, total motility and forward progression, normal morphology, and vitality were significantly lower in patients with acromegaly than in controls. After 6 months, 22 patients achieved disease control after surgery (n 11) or LAN (n 11), whereas 13 had uncontrolled disease. Serum T and DHT levels and sperm number significantly increased in all groups. FSH and LH levels and total motility increased only in patients achieving disease control. Posttreatment IGF-I levels significantly correlated with total motility (r – 0.45; P 0.006). In conclusion, short-term GH and IGF-I suppression after surgery or LAN significantly increased T and DHT levels and improved sperm number and motility in acromegalic men. (J Clin Endocrinol Metab 87: 4193– 4197, 2002)

The effects of different doses of transdermal estradiol (TE) on bone mineral density (BMD) in a man with aromatase deficiency were evaluated. The study protocol was divided in the following four phases: phase 1, before estradiol treatment; phase 2, 50 μg TE twice weekly for 6 months; phase 3, 25 μg TE twice weekly for 9 months; and phase 4, 12.5 μg TE twice weekly for 9 months. X-rays of hands, legs, and pelvis were performed, and BMD of the lumbar spine, hormonal parameters (LH, FSH, testosterone, and estradiol), and markers of bone turnover were determined during each phase.BMD in phase 1 was 0.933 g/cm2 and increased to 1.051 and 1.173 g/cm2 after 4 and 7 months of TE, respectively. In phase 3, BMD reached the maximum value (1.275 g/cm2). In phase 4, BMD decreased to 1.180 g/cm2 and was 1.029 g/cm2 at the end of the study protocol. A bilateral necrosis of femoral heads was also detected by x-ray films.In phase 1 serum testosterone was in the normal range, whereas serum estradiol was undetectable. During the 24-month period of treatment with TE (phases 2–4), estradiol was directly related to the amount of TE, whereas LH was inversely related to estradiol serum levels. Estradiol and gonadotropins reached optimal values only in phase 3, when FSH also was near normal; serum testosterone concentrations were normal in phases 3 and 4.This study confirms the role of estrogens in achieving and maintaining bone mineral content in the human male, providing further clinical tools useful in the management of bone loss in aromatase deficiency in the male. We suggest that the adequate substitutive dose of TE for maintaining both bone mass and normal estradiol serum levels in adult men with aromatase deficiency may be 25 μg twice weekly (0.47 μg/kg weekly).

Treatment of osteoporosis is aimed to prevent fragility fractures and to stabilize or increase bone mineral density. Several drugs with different efficacy and safety profiles are available. The long-term therapeutic strategy should be planned, and the initial treatment should be selected according to the individual site-specific fracture risk and the need to give the maximal protection when the fracture risk is highest (i.e. in the late life). The present consensus focused on the strategies for the treatment of postmenopausal osteoporosis taking into consideration all the drugs available for this purpose. A short revision of the literature about treatment of secondary osteoporosis due both to androgen deprivation therapy for prostate cancer and to aromatase inhibitors for breast cancer was also performed. Also premenopausal females and males with osteoporosis are frequently seen in endocrine settings. Finally particular attention was paid to the tailoring of treatment as well as to its duration. Electronic supplementary material The online version of this article (doi:10.1007/s40618-016-0434-8) contains supplementary material, which is available to authorized users.