Virilization by an Ovarian Tumor: Presentation Is Not Always Acute.

Androgen-producing steroid cell ovarian tumors are rare, comprising less than 1% of ovarian neoplasms, and can present with infertility and rapid virilization. Here we discuss the case of a 28-year-old woman who presented with an unusually insidious 2-year history of infertility, hirsutism, and clitoromegaly who was found to have an elevated serum testosterone and a left ovarian mass. She underwent oophorectomy and pathology revealed a steroid cell tumor, not otherwise specified (NOS), with no malignant features. Following surgery, the patient's hyperandrogenic symptoms resolved with normalization of testosterone within 6 months, and she was able to conceive spontaneously. In reproductive-aged women with progressive hyperandrogenic symptoms, androgen-producing tumors, including those of ovarian origin, should be suspected. Thorough investigation, including plasma hormone levels and tumor histology, can lead to accurate diagnosis and management. Treatment should be guided by histology and surgical staging, with consideration for future fertility desires. Women who have not completed childbearing can undergo unilateral oophorectomy or tumor resection for benign tumors, with close monitoring of sex hormone levels postoperatively.

Multiple concomitant life-threatening opportunistic infections due to uncontrolled hypercortisolism.

Opportunistic infections associated with severe cortisol excess carry a high mortality rate and are most prevalent with ectopic ACTH syndrome. There are limited reports of these cases described in the literature. In this case report, we describe multiple severe life-threatening opportunistic infections due to endogenous hypercortisolism. Our patient, against numerous expectations, survived multiple opportunistic infections including disseminated invasive aspergillosis, Cytomegalovirus endophthalmitis and Pneumocystis Jirovecii pneumonia, reinforcing the need for multidisciplinary care for patients presenting with complicated hypercortisolism.

Sodium Perturbations After Pituitary Surgery.

Sodium perturbations are a common complication after pituitary surgery, with hyponatremia being the most frequent. Postoperative assessments should be tailored to the early and late periods, and monitoring sodium perturbations is recommended. Cerebral salt wasting is rare after pituitary surgery, and diagnosis and management can be challenging. Providing patient counseling and close postoperative follow-up is important to effectively manage diabetes insipidus and reduce hospital readmissions due to sodium perturbations.

Decreased quality of life (QoL) in hypopituitary patients: involvement of glucocorticoid replacement and radiation therapy.

PURPOSE: Hypopituitary patients are assumed to have decreased QoL due to GHD. However, in placebo controlled trials, the effects of GH replacement are no different from placebo. Hydrocortisone dose > 20 mg/day and pituitary radiation are independently associated with poorer QoL. We assessed QoL in panhypopituitary GH- deficient patients never treated with GH. METHODS: Study group was divided into: (a) surgery followed by radiation (n = 21) and (b) surgery alone (n = 32). Mean duration of GHD was 71.4 ± 7.8 months and mean daily hydrocortisone dose was 15 ± 0.7 mg. Control group had transnasal surgery for benign sinus conditions (n = 54). RESULTS: AGHDA scores were significantly worse in the entire study group compared to controls (8.1 ± 1.0 vs. 5.1 ± 0.9, p = 0.03). In patients with history of radiation therapy AGHDA scores were significantly worse than in controls (9.1 ± 1.5, p = 0.02) and SNOT-22 (Sino-Nasal Outcome Test) scores were also significantly worse (15.8 ± 2.0 vs. 23.2 ± 3.5, p = 0.04). However, AGHDA scores in patients without history of radiation and on "physiological" dose of hydrocortisone were similar to those in controls (5.1 ± 0.9 vs. 7.3 ± 1.3, p = 0.17). CONCLUSIONS: Replacement with hydrocortisone doses not exceeding 20 mg/day and avoidance of radiation therapy was accompanied by normal QoL in patients not replaced with GH. Thus, we suggest that the decreased QoL in hypopituitary patients may not be due to GH deficiency per se, but rather to high hydrocortisone doses and to aftereffects of cranial radiation.

Genetics of Combined Pituitary Hormone Deficiency: Roadmap into the Genome Era.

The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular diagnosis of this disorder is valuable for predicting disease progression, avoiding unnecessary surgery, and family planning. We expect that the application of high throughput sequencing will uncover additional contributing genes and eventually become a valuable tool for molecular diagnosis. For example, in the last 3 years, six new genes have been implicated in CPHD using whole-exome sequencing. In this review, we present a historical perspective on gene discovery for CPHD and predict approaches that may facilitate future gene identification projects conducted by clinicians and basic scientists. Guidelines for systematic reporting of genetic variants and assigning causality are emerging. We apply these guidelines retrospectively to reports of the genetic basis of CPHD and summarize modes of inheritance and penetrance for each of the known genes. In recent years, there have been great improvements in databases of genetic information for diverse populations. Some issues remain that make molecular diagnosis challenging in some cases. These include the inherent genetic complexity of this disorder, technical challenges like uneven coverage, differing results from variant calling and interpretation pipelines, the number of tolerated genetic alterations, and imperfect methods for predicting pathogenicity. We discuss approaches for future research in the genetics of CPHD.

Gene Expression in Mouse Thyrotrope Adenoma: Transcription Elongation Factor Stimulates Proliferation.

Thyrotrope hyperplasia and hypertrophy are common responses to primary hypothyroidism. To understand the genetic regulation of these processes, we studied gene expression changes in the pituitaries of Cga(-/-) mice, which are deficient in the common α-subunit of TSH, LH, and FSH. These mice have thyrotrope hypertrophy and hyperplasia and develop thyrotrope adenoma. We report that cell proliferation is increased, but the expression of most stem cell markers is unchanged. The α-subunit is required for secretion of the glycoprotein hormone ß-subunits, and mutants exhibit elevated expression of many genes involved in the unfolded protein response, consistent with dilation and stress of the endoplasmic reticulum. Mutants have elevated expression of transcription factors that are important in thyrotrope function, such as Gata2 and Islet 1, and those that stimulate proliferation, including Nupr1, E2f1, and Etv5. We characterized the expression and function of a novel, overexpressed gene, transcription elongation factor A (SII)-like 5 (Tceal5). Stable expression of Tceal5 in a pituitary progenitor cell line is sufficient to increase cell proliferation. Thus, Tceal5 may act as a proto-oncogene. This study provides a rich resource for comparing pituitary transcriptomes and an analysis of gene expression networks.

The effect of somatostatin analogs on vitamin D and calcium concentrations in patients with acromegaly.

PURPOSE: The goals of this study were to determine: (1) 25OH vitamin D (25OHD) and calcium levels in patients with acromegaly and their association with insulin-like growth factor (IGF-1) and (2) whether somatostatin analog (SSA) therapy effects calcium and 25OHD levels. METHODS: 125 patients with acromegaly were studied. Serum calcium and 25OHD levels were compared prior to and after vitamin D supplementation between patients receiving versus not receiving SSA in whom medical therapy included pegvisomant and/or dopamine agonists. Calcium and 25OHD levels were also evaluated longitudinally prior to and during short-term (mean 3 months, range 1-5) and long-term (mean 49 months, range 7-180) SSA administration. Vitamin D2 50,000 units weekly were given to 3 patients in the cross sectional and 1 in the longitudinal group; 400-4,000 units/day of D3 were given to 11 and 5 in respective groups. RESULTS: In patients with a comparable mean IGF-1 index and season of testing, mean serum levels of 25OHD prior to vitamin D supplementation did not differ in patients receiving versus not receiving SSA (30 ± 3 vs. 30 ± 1 ng/ml, p = 0.99) and the prevalence of vitamin D sufficiency was similar between SSA and non SSA groups (42 vs. 57%, p = 0.20), prior to vitamin D supplementation. In patients with a comparable mean IGF-1 index and season of testing, mean serum 25OHD levels in patients increased after vitamin D supplementation in both those who were (37 ± 2 ng/ml, N = 23, p = 0.007) and were not receiving SSA (35 ± 1 ng/ml, N = 69, p = 0.005) compared to pre-D supplementation levels but were not different between these groups, p = 0.95) after D supplementation. Calcium and albumin were normal throughout longitudinal follow up. Calcium correlated with IGF-1 index (ρ = 0.29, p = 0.001, N = 125). In the longitudinal subset, serum calcium decreased transiently, in patients receiving short-term SSA (pretreatment 9.9 ± 0.1 mg/dl vs. short-term SSA 9.5 ± 0.1, p = 0.004). After long-term SSA therapy, calcium increased compared to levels on short-term therapy (9.8 ± 0.1 mg/dl vs. 9.5 ± 0.1, p = 0.017) and were unchanged compared to baseline. Mean vitamin D levels were sufficient at baseline prior to SSA therapy (33 ± 5.0 ng/ml), and did not change during short term (29 ± 6 ng/ml, p = 0.85) and long term SSA therapy (35 ± 5 ng/ml, p = 0.43). CONCLUSIONS: Prior to and after vitamin D supplementation, patients with acromegaly receiving long-term SSA had vitamin D levels similar to those receiving other therapies, suggesting that long-term SSA therapy does not affect serum vitamin D. However, given the limitations of this retrospective study, further prospective studies evaluating the impact of SSA on vitamin D levels are necessary to confirm these findings definitively. Calcium levels are positively associated with IGF-1 index in patients with acromegaly. There is a transient decrease in calcium levels with short-term SSA use. The acute effect of SSA on calcium does not appear to be mediated by albumin, 25OHD or PTH and resolves with long-term SSA treatment. The transient decrease in calcium with short-term SSA use resolved with long-term SSA therapy.

Psychotropic-induced hyperprolactinemia: a clinical review.

BACKGROUND: Psychotropic medications, particularly select antipsychotics, are a common cause of drug-induced hyperprolactinemia. As high prolactin may be associated with hypogonadism, reproductive dysfunction, and bone loss, it is important to recognize this condition and understand its management. OBJECTIVE: The aim of this review is to evaluate the causes, signs, and symptoms associated with hyperprolactinemia, to describe mechanisms through which psychotropic medications elevate prolactin, and to suggest an evidence-based management approach for patients with psychotropic drug-induced hyperprolactinemia. METHODS: A PubMed/MEDLINE search was conducted on the topic of psychotropic agents as a cause of hyperprolactinemia. The material with most relevance to current psychiatric practice and of highest level of evidence was included in this review. CONCLUSION: Hyperprolactinemia should be evaluated in adult patients receiving psychotropic agents if signs and symptoms associated with hyperprolactinemia are present. It is also important to exclude pituitary and hypothalamic disease by magnetic resonance imaging if hyperprolactinemia is not definitely caused by psychotropic medications. As bone loss may occur because of hyperprolactinemia-mediated hypogonadism, bone mineral density (BMD) should be evaluated in patients with persistent high prolactin and reproductive dysfunction. Aripiprazole or other prolactin-sparing atypical antipsychotics may be alternatives or aripiprazole can be considered as adjunctive therapy in select cases of psychotropic-induced hyperprolactinemia.

Effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on hemoglobin levels.

BACKGROUND: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely used in the management of congestive heart failure (CHF), diabetes mellitus (DM) and hypertension (HTN). Use of these agents is reported to cause anemia. METHODS: We examined the association between standard care use of ACEI or ARB and subsequent change in hemoglobin (Hgb) in a population of 701 adult primary care patients with DM, CHF and/or HTN. Data analysis was conducted to adjust for baseline differences between the treatment groups. RESULTS: After adjusting for differences in covariates at baseline between the subjects who were prescribed ACEI (N = 519) and ARB (N = 182), as well as the associated odds of being prescribed ARB, the ACEIs were associated with lower mean Hgb [0.18 (0.02, 0.34) g/dL, p = 0.02] at follow up relative to ARBs. However, patients with CHF experienced an increase in Hgb while on treatment (0.42 g/dL), especially those treated with ACEIs (0.56 g/dL). Chronic kidney disease at baseline was not associated with a significant decrease in Hgb in either treatment group. CONCLUSIONS: Since ACEIs and ARBs are most frequently used in patients who are vulnerable to complications from anemia, such as patients with CHF, HTN and DM, these findings may be useful to clinicians in selecting medications and monitoring patients for the adverse effects of treatment.