Ovarian Hilus-Cell Hyperplasia and High Serum Testosterone in a Patient With Postmenopausal Virilization

ObjectiveTo describe a woman with postmenopausal virilization and hirsutism caused by hilus-cell hyperplasia.MethodsWe present a case report including laboratory, radiographic, and pathologic findings in a patient with postmenopausal hirsutism and virilization caused by ovarian hilus-cell hyperplasia as well as a brief review of the literature.ResultsA 60-year-old postmenopausal woman presented with extensive hirsutism, male-pattern hair loss, and clitoromegaly. The patient’s plasma testosterone levels were very high, but computed tomography showed the adrenal glands to be normal in size. Pelvic ultrasonography revealed a cystic lesion in the left ovary. After bilateral salpingo-oophorectomy, histologic examination demonstrated a diffuse pattern of hilus-cell hyperplasia in the ovarian hilum.ConclusionIn the differential diagnosis of postmenopausal virilization, hilus-cell hyperplasia, although rare, should be considered.     

Hyperandrogenism Due to a Testosterone-Secreting Sertoli-Leydig Cell Tumor Associated With a Dehydroepiandrosterone Sulfate-Secreting Adrenal Adenoma in a Postmenopausal Woman: Case Presentation and Review of Literature

ObjectiveTo report a case of hyperandrogenism attributable to the presence of an adrenal adenoma secreting dehydroepiandrosterone sulfate (DHEA-S) and an ovarian Sertoli-Leydig cell tumor secreting testosterone in a postmenopausal woman.MethodsThe laboratory, radiologic, and pathologic findings in our case are described. In addition, the pertinent literature is reviewed.ResultsA 56-year-old woman presented with a history of gradual increase in facial and body hair, scalp hair loss, male pattern baldness, and deepening of her voice, beginning a few years after spontaneous menopause at age 49 years. She had hypertension, obesity, and type 2 diabetes mellitus. Laboratory tests showed elevated levels of total testosterone (348 ng/dL) and DHEA-S (2,058 μg/dL), and a left adrenal tumor (3 by 4 cm) was detected on abdominal computed tomographic scan. Laparoscopic left adrenalectomy was performed, and the pathologic diagnosis was adrenal adenoma. The DHEA-S returned to normal levels, but the serum testosterone concentration remained elevated. Transvaginal ultrasonography disclosed an ovarian tumor. Bilateral oophorectomy was performed, and an ovarian Sertoli-Leydig cell tumor was diagnosed. The hormonal and clinical picture normalized after this surgical intervention.ConclusionAfter extensive review of the literature, we believe that this is the first reported case of a coincidental DHEA-S-secreting adrenal adenoma and a testosterone-secreting ovarian Leydig cell tumor causing signs of virilization. (Endocr Pract. 2009;15:149-152)     

Management of hyperandrogenism in adolescent girls.

Hyperandrogenism in adolescent girls can be a troubling problem because of the difficulty in establishing a diagnosis and in prescribing appropriate therapy. Androgen excess in adolescent patients encompasses a spectrum of clinical presentations, including acne, hirsutism, oligomenorrhea, amenorrhea, virilism, and ovarian cysts. Androgen excess is a clinical and chemical feature of idiopathic hirsutism, late-onset forms of congenital adrenal hyperplasia, and polycystic ovarian disease; in some cases, functional hyperandrogenism is discussed. We recommend screening for hyperandrogenism by measuring blood levels of testosterone, dehydroepiandrosterone sulfate, and delta 4-androstenedione, while others propose a first dexamethasone suppression test for evaluation of free testosterone, dehydroepiandrosterone sulfate, and cortisol. Treatment will be chosen according to particular symptoms such as acne, hirsutism, obesity, or oligomenorrhea.     

Novel Endocrine Disrupter Effects of Classic and Atypical Antipsychotic Agents and Divalproex: Induction of Adrenal Hyperandrogenism,Reversible with Metformin or Rosiglitazone

ObjectiveTo ascertain an association between the a priori known insulin resistance caused by antipsychotic agents and divalproex and adrenal hyperandrogenism and to determine whether the associated hyperandrogenism is reversible with insulin sensitizers.MethodsWe studied 26 consecutive psychiatric inpatients (22 women and 4 men) receiving the aforementioned medications, who were referred to us for a consultation. They ranged in age from 19 to 79 years and had a mean body mass index (SEM) of 32.35 ± 1.26 kg/m². Between 8 AM and 9 AM, blood samples were collected for 17-hydroxyprogesterone, 17-hydroxypregnenolone, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulfate, 11-deoxycortisol, luteinizing hormone and follicle-stimulating hormone (in reproductive age women), estrone, estradiol (in reproductive age women), free testosterone (in women), deoxycorticosterone, and sex hormone-binding globulin (SHBG), which were measured by radioimmunoassay, after chromatography if necessary. For intact, premenopausal women, measurement of the abnormal steroid metabolite or SHBG level was repeated during prednisone therapy (5 mg at bedtime) to document the likely adrenal origin of the abnormality. Men, women who had undergone bilateral oophorectomy, and postmenopausal women had hyperandrogenism of adrenal origin by default. Clinical features included central obesity, acanthosis, hirsutism, alopecia, type 2 diabetes mellitus, and oligomenorrhea.ResultsWe found reversed estrone/estradiol ratios in 4 patients, decreased SHBG in 4, increased 17-hydroxypregnenolone in 8, increased 17-hydroxyprogesterone in 2, increased deoxycorticosterone in 2, increased DHEA sulfate in 1, increased 11-deoxycortisol in 4, increased androstenedione in 1, and reversed ratios of luteinizing hormone to follicle-stimulating hormone in 2. The biochemical abnormalities were corrected in 8 of 8 patients receiving metformin and in 2 of 2 patients receiving rosiglitazone.ConclusionInsulin resistance caused by antipsychotic agents and divalproex is associated with adrenal hyperandrogenism. Metformin and rosiglitazone correct the biochemical abnormalities detected without compromising their psychotropic effect. Adrenal androgen synthesis may be increased by hyperinsulinemia-induced hyperphosphorylation of P450c17α, resulting in an increase in its 17,20-lyase activity, which magnifies the effects of any distal steroidogenic enzyme defects. Treatment with metformin or rosiglitazone prevents excess adrenal androgen synthesis. (Endocr Pract. 2007; 13:601-608)     

Virilizing Ovarian Leydig Cell Tumor in A Woman with Subclinical Cushing Syndrome

ObjectiveTo report the case of a patient with a virilizing ovarian Leydig cell tumor and subclinical Cushing syndrome attributable to an adrenal adenoma.MethodsDetailed clinical, laboratory, radiologic, and pathologic findings are presented, and the pertinent literature is reviewed.ResultsA 49-year-old woman was referred for evaluation of a left adrenal mass (3.0 by 2.4 cm), which had been diagnosed by computed tomographic scan 4 years previously during a work-up for hirsutism. On examination, she had central obesity, facial hirsutism, and male pattern baldness. Work-up showed elevated total and free testosterone levels of 196 ng/dL (reference range, 20 to 70) and 24 pg/mL (1 to 9), respectively. Other results (and reference ranges) were as follows: dehydroepiandrosterone sulfate, 7.5 μg/dL (10 to 221); corticotropin, 12 pg/mL (5 to 50); morning cortisol, 1.4 μg/dL after a 1-mg overnight dexamethasone suppression test; and urine free cortisol, 48.8 μg/24 h (20 to 100). The testosterone level decreased by 14% after a 2-day low-dose dexamethasone suppression test. Findings on transvaginal ovarian ultrasonography and a computed tomographic scan of the pelvis were normal. A laparoscopic adrenalectomy revealed an adrenal adenoma. On the first day postoperatively, the cortisol level was less than 1.0 μg/dL; however, the testosterone level remained elevated. At 6 months postoperatively, a normal result of a cosyntropin stimulation test indicated recovery of the hypothalamic-pituitaryadrenal axis. Bilateral oophorectomy revealed a 1.3-cm right ovarian Leydig cell tumor. Postoperatively, the testosterone level declined to less than 20 ng/dL.ConclusionTo our knowledge, this is the first case report of a virilizing ovarian Leydig cell tumor in a patient with subclinical Cushing syndrome. (Endocr Pract. 2008;14:358-361)     

Virilizing Adrenal Ganglioneuroma in a Woman with Subclinical Cushing Syndrome

ObjectiveTo describe a patient with a virilizing adrenal ganglioneuroma and subclinical Cushing syndrome.MethodsDetailed clinical, laboratory, radiologic, and pathologic findings are presented, and the pertinent literature is reviewed.ResultsA 56-year-old postmenopausal woman was referred for evaluation of a 3.6- by 3.0-cm right adrenal mass, which had been diagnosed during a work-up for hirsutism. A bilateral oophorectomy done 2 months before the presentation failed to correct the elevated testosterone levels. On examination, she had severe hirsutism on her face, chest, back, and extremities, as well as male pattern baldness and clitoromegaly. Biochemical evaluation showed elevated total and free serum testosterone levels of 319 ng/dL (reference range, 20 to 70) and 78 pg/mL (reference range, 1 to 9), respectively, values in the adult male range. The serum dehydroepiandrosterone sulfate level was 117 μ/dL (reference range, 10 to 152), and the urine free cortisol was 10.4 μg/24 h (reference range, < 45). A laparoscopic adrenalectomy revealed a 5.0-cm adrenal ganglioneuroma containing nests of adrenocortical cells. On the first day postoperatively, the serum cortisol level was < 1.0 μg/dL. At 1 month after adrenalectomy, the total and free testosterone levels had declined to 16 ng/dL and 3.1 pg/mL, respectively. At 2 months postoperatively, normal results of a cosyntropin stimulation test (basal and peak cortisol levels of 13.6 and 20.0 μg/dL, respectively) indicated recovery of the hypothalamic-pituitary-adrenal axis.ConclusionTo our knowledge, this is the first case report of a virilizing adrenal ganglioneuroma with this unique pathologic finding and concomitant subclinical Cushing syndrome. (Endocr Pract. 2008;14:584-587)     

Management of Fully Pubertal Girls With Nonclassical Congenital Adrenal Hyperplasia: Glucocorticoids Versus Oral Contraceptives

ObjectiveTo compare clinical outcomes of 3 treatment regimens—glucocorticoids (GCs), oral contraceptives (OCs), or a combination of both—administered to adolescents and young women diagnosed in childhood with nonclassical congenital adrenal hyperplasia (NCCAH), who had been treated with GCs until their adult height was achieved.MethodsA retrospective study of medical records of 53 female patients with NCCAH followed in 3 tertiary pediatric endocrinology institutes. The 3 treatment groups were compared for the prevalence of hirsutism and acne, standardized body mass index (BMI)-standard deviation score (SDS), and androgen levels at the attainment of adult height (baseline), 1-year later, and at the last documented visit.ResultsAt baseline, there were no significant differences among groups in BMI-SDS, androgen levels, hirsutism prevalence, acne, or irregular menses. From baseline to the last visit, the rate of hirsutism declined significantly only in the OC group (37.5% vs 6.2%, respectively; P = .03). The rate of acne declined in the combined group (50% vs 9%, respectively; P = .03) with a similar tendency in the OC group (50% vs 12.5%, respectively; P = .05). No significant changes were observed in BMI-SDS for the entire cohort or any subgroup during follow-up. A significant rise in androstenedione (P < .001), testosterone (P < .01), and 17-hydroxyprogesterone (P < .01) levels was observed only in the OC group.ConclusionIn girls diagnosed in childhood with NCCAH, who require treatment for hyperandrogenism following completion of linear growth, management should be tailored individually using a patient-centered approach. Treatment with OCs might be better than that with GCs for regression of hirsutism and acne. The long-term effects of elevated levels of androgens associated with this treatment regimen should be further studied.     

Hirsutism: Diagnosis and management

Background:Hirsutism is defined as excess hair growth in androgen-dependent areas of the body in women.Objective: This article provides an updated review of hirsutism, focusing on the etiologies, clinical features, approach to diagnostic evaluation, and treatment options.Methods: The PubMed database was searched for English-language articles published from 1981 to the present, using the terms hirsutism, polycystic ovarian syndrome, congenital adrenal hyperplasia, hirsutism diagnosis, and hirsutism treatment. Reference lists from review articles on hirsutism during this time period were also examined.Results: While there are many causes of hirsutism, the majority of patients have a benign process that may be idiopathic. In some circumstances, hirsutism is a sign of functional ovarian hyperandrogenism or congenital adrenal hyperplasia. Even more rarely, it is the presenting sign of an internal malignancy.Conclusions: Hirsutism clinically presents in women as excessive hair growth in androgen-dependent areas. It is a particularly important diagnosis to make, because it often significantly affects a woman's perception of her femininity and less commonly can be a sign of an underlying malignancy or a cutaneous manifestation of a condition with significant cardiovascular or other morbidity. A variety of treatments exist to help minimize the appearance of unwanted hair.     

Investigative strategy of hyperandrogenism in women

Investigative procedures in the assessment of female hyperandrogenism are reviewed. Based on their experience, the authors suggest an inexpensive investigative strategy in hyperandrogenic females consisting of the following: the first step depends upon the clinical symptoms--in cases of hirsutism with regular menstrual cycles, plasma testosterone (T) and plasma dehydroepiandrosterone sulfate (DHA-S) are assayed, and the basal body temperature chart is recorded. In cases of hirsutism with irregular or anovulatory menstrual cycles, in addition to T and DHA-S, plasma 17-hydroxyprogesterone and urinary-free cortisol are assayed. In case of anovulation without hirsutism, T and DHA-S are assayed, and the LHRH test is performed. The results of this first investigation allow to attribute to the woman one of the six following hormone profiles: (1) metabolic hyperadrenalism; (2) tumoral hyperandrogenism; (3) 21-hydroxylase defect; (4) nontumoral DHA-S increase; (5) nontumoral ovarian hyperandrogenism; (6) idiopathic hirsutism. The additional investigative procedures required in each of these groups are detailed.     

13-cis-Retinoic Acid (Isotretinoin) Unmasking of Clinical Polycystic Ovary Syndrome

ObjectiveTo describe a woman in whom polycystic ovary syndrome manifested during treatment with 13-cis-retinoic acid (isotretinoin) for severe acne.MethodsWe present serial clinical and biochemical findings for a several month period before, during, and after therapy with 13-cis-retinoic acid. Homeostasis model assessment of insulin resistance was calculated from the fasting plasma glucose and insulin concentrations.ResultsA 32-year-old woman with some past features suggestive of metabolic syndrome took 13-cis-retinoic acid for 20 weeks as treatment of nodulocystic acne. During therapy, amenorrhea and hirsutism developed, as well as biochemical evidence of hyperandrogenemia and insulin resistance, as assessed by homeostasis model assessment of insulin resistance. After discontinuation of the medication, both the clinical features and the laboratory abnormalities resolved.Conclusion13-cis-Retinoic acid likely causes insulin resistance through its role as an agonist of retinoid A and X receptors. Although elevated levels of serum triglycerides are well documented with use of this drug, to the best of our knowledge this is the first report of a patient in whom polycystic ovary syndrome, a condition known to be associated with insulin resistance, manifested during isotretinoin therapy. (Endocr Pract. 2007;13: 776-779)     

Strategic approach of hyperandrogenism in women

Based on the results of the laboratory screening of 35 hirsute patients, a strategic approach of hyperandrogenism is proposed. The determination of plasma concentration of total testosterone (T), androstenedione (A) and dehydroepiandrosterone sulfate (DHEAS) appeared to be the basic investigation before to further explore the adrenal (ACTH test) and/or ovarian (gonadotropin measurements) androgen secretion. Together with the clinical findings, plasma T, A and DHEAS levels generally bring evidence of androgen-secreting tumors or polycystic ovaries, or suggest the possibility of adrenal hyperplasia. In the other cases, only the determination of plasma unbound T level is useful for demonstrating the hyperandrogenism. Finally in patients with 'so-called' idiopathic hirsutism, while evidence of excessive androgen production can be obtained by the laboratory screening, the origin of this hyperandrogenism remains uncertain in most cases.     

Sertoli-Leydig cell tumor - a rare androgen secreting ovarian tumor in postmenopausal women. Case report and review of literature

Sertoli-Leydig cell tumors (SLCT) constitute only 1-0.5% of all primary ovarian neoplasms. We report a SLCT in a postmenopausal woman aged 69 years. The physical examination revealed severe hirsutism. Basal hormonal evaluation showed high plasma testosterone and estradiol values, with suppressed plasma gonadotropins. Computer tomograph scan revealed a right ovarian tumor mass of 4,3/3 cm, confirming an androgen secreting ovarian tumor. The histopathological and immunocytochemical examination established the diagnosis of well differentiated Sertoli-Leydig cell tumor. The tumor was positive for cytokeratin KL 1 and S-100 protein and, in isolated tumor cells, positive for alpha-fetoprotein. Postsurgical evolution was favorable; controls after 6 months and 3,5 years showed marked reduction of hirsutism, normal plasma testosterone values and gonadotropins in normal postmenopausal range. We discuss the complex aspects of etiology and pathogenesis, the clinical and hormonal settings, the role of immunocytochemical markers in diagnosis, as well as the therapy and the prognostic features of this ovarian tumor.     

The Hirsute Woman: Challenges in Evaluation and Management

ObjectiveTo review the etiology, pathogenesis, diagnostic approach, and management of hirsutism.MethodsWe discuss the clinical course of hirsutism and provide our recommendations on the various treatment options available.ResultsHirsutism is a common clinical problem characterized by the presence of increased terminal hair growth in androgen-dependent areas of the skin. The development of hirsutism depends on the presence of the pilosebaceous unit, which is genetically determined, as well as the presence of the androgen receptor and intracellular 5α-reductase activity, which converts testosterone to its more active metabolite, dihydrotestosterone. A detailed history and physical examination and the following laboratory tests can diagnose most causes of hirsutism: early-morning follicular phase measurement of total testosterone, testosterone not bound to sex hormone-binding globulin, dehydroepiandrosterone sulfate, 17-hydroxypro- gesterone, prolactin, and thyrotropin levels. Oral contraceptive preparations may be effective monotherapy formild hirsutism. For the treatment of more severe hirsutism, oral contraceptive pills combined with spironolactone are as effective as oral contraceptive pills containing cyproter- one acetate, which are not available in the United States. Because of teratogenicity, spironolactone should be used with caution in premenopausal women when it is administered without an oral contraceptive pill. Metformin is an alternative therapy for hirsutism in women with polycystic ovary syndrome who have other indications for metformin use. Metformin is not as effective as antiandrogens for the management of hirsutism. The use of glucocorticoids, finasteride, or flutamide is not recommended.ConclusionsHirsutism can be evaluated with a detailed history and physical examination and a limited number of hormonal tests. Serious disorders presenting as hirsutism are rare and can be excluded with the recommended evaluation. Treatment is targeted at reducing the production and bioavailability of testosterone, as well as blocking target tissue androgen action. (Endocr Pract. 2011;17:807-818)     

Metformin-Responsive Classic Salt-Losing Congenita L Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: a Case Report

ObjectiveTo study the effect of adding metformin to standard steroid replacement therapy in a patient with classic salt-losing congenital adrenal hyperplasia due to 21- hydroxylase deficiency with suboptimal biochemical and clinical control.MethodsWe present the clinical and laboratory findings before and after the addition of metformin to the therapeutic regimen of the study patient.ResultsA 17-year-old girl had been diagnosed as a neonate with classic salt-losing congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (CYP21A2 deficiency). She was treated with hydrocortisone, 20 mg in the morning and 10 mg at bedtime, and fludrocortisone, 50 mcg daily. While on steroid replacement, she maintained normal serum electrolytes, glucose, blood pressure, and external genitalia, but she continued to express clinical features of obesity, hirsutism, amenorrhea, and acanthosis nigricans. Elevated laboratory measurements included the following: fasting 17-hydroxyprogesterone, 3410 ng/dL; total testosterone, 326 ng/dL; and androstenedione, 390 ng/dL. She was initiated on metformin, 500 mg twice daily after meals. After 3 months, the patient lost 2 kg, amenorrhea resolved, 17-hydroxyprogesterone decreased to 1539 ng/dL, total testosterone decreased to 163 ng/dL, and androstenedione levels remained unchanged.ConclusionsMetformin, an agent known to reduce insulin resistance, further suppressed the 17-hydroxyprogesterone concentration in a patient with classic congenital adrenal hyperplasia on steroid replacement therapy. Metformin may improve clinical and biochemical outcomes in classic congenital adrenal hyperplasia without the risk of iatrogenic Cushing syndrome. (Endocr Pract. 2008;14:889-891)     

Concomitant Secretion of Glucocorticoid,Androgens, and Mineralocorticoid by an Adrenocortical Carcinoma: Case Report and Review of Literature

ObjectiveTo present a case of concomitant secretion of cortisol, androgens, and 11-deoxycorticosterone (DOC) by an adrenocortical carcinoma and review the literature in an attempt to identify similar cases.MethodsThe patient’s medical history, physical examination, laboratory data, computed tomographic scan, and histopathologic results were analyzed and summarized in a case report, and an extensive review of the literature was performed.ResultsEndocrinologic data showed excess cortisol production, substantially elevated testosterone and androstenedione levels, and profoundly increased DOC in the setting of suppressed aldosterone. An abdominal computed tomographic scan showed a left adrenal tumor. A left adrenalectomy was performed, and the histopathologic diagnosis was stage II adrenocortical carcinoma. The review of the pertinent literature revealed the absence of any identical cases in the past.ConclusionOur patient presented with a rare case of cosecretion of cortisol, testosterone, androstenedione, and DOC by an adrenocortical carcinoma, resulting in a clinical picture consistent with Cushing’s syndrome, hyperandrogenism, and primary hypermineralocorticoidism. We recommend the routine performance of a DOC assay in the setting of mineralocorticoid excess in association with low plasma aldosterone levels. (Endocr Pract. 2007;13: 408-412)     

Some Clues and Pitfalls in the Diagnosis of Acromegaly

ObjectiveTo describe a case of acromegaly in a young woman using oral contraceptives who had nonspecific symptoms and persistent hyperphosphatemia and to analyze the reasons for delay in diagnosis.MethodsA 31-year-old woman underwent evaluation for failure of menstrual flow to resume after discontinued use of oral contraceptives. Clinical and laboratory findings are summarized, and atypical manifestations of acromegaly are discussed.ResultsThe patient complained of weight gain, acne, and increased facial hair growth, and laboratory tests showed a low estradiol level and hyperinsulinemia. “Postpill amenorrhea” and polycystic ovary syndrome were considered possible diagnoses. During subsequent endocrinology consultation, hyperphosphatemia was present on three occasions during a 7-month period. Hormonal studies for evaluation of pituitary function revealed increased insulin-like growth factor-I and growth hormone (GH) levels. Acromegaly was suspected, and the increased GH level failed to suppress after a glucose load. Magnetic resonance imaging revealed a pituitary macroadenoma with suprasellar extension. Visual field testing showed bitemporal abnormalities. Transsphenoidal resection successfully removed the GH-producing tumor, and hormone replacement therapy was initiated postoperatively.ConclusionThe textbook presentation of GH excess is a late feature of acromegaly. The diagnosis in a young woman can be easily missed when clinicopathologic findings are not classic and the picture is further clouded by factors such as oral contraceptive use. Features may also resemble polycystic ovary syndrome, a more common condition in women of childbearing age. This case also illustrates that hyperphosphatemia, overlooked in this patient, can precede the full-blown clinical manifestations of acromegaly and serve as a subtle clue to the underlying disease. Awareness of these situations and screening for high GH levels in patients with unexplained, persistent hyperphosphatemia are advisable for making an early correct diagnosis and providing appropriate therapy. (Endocr Pract. 2004;10:348-352)     

Over Hypothyroidism in a Woman Undergoing Controlled Ovarian Hyperstimulation

ObjectiveThyroid function and gonadal axis are related throughout a woman’s fertile period. Modifications of thyroid hormone levels have been reported as a consequence of controlled ovarian stimulation for infertility.MethodsA 28-year-old woman with regular menses and previous evidence of euthyroidism underwent controlled ovarian hyperstimulation (COH) for assisted reproductive technology (ART). Free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), and autoantibodies against thyroperoxidase and thyroglobulin (TPOAb and TgAb, respectively) were measured before COH. FT4, FT3, and TSH were re-evaluated 6 days, 2 weeks (during oocyte retrieval), and 1 month after the beginning of the procedure.ResultsThe baseline evaluation revealed subclinical autoimmune hypothyroidism. The patient was hypothyroidic at 6 days and 2 weeks and spontaneously returned to euthyroidism 1 month after COH.ConclusionThis is the first case of a woman with an unknown subclinical autoimmune hypothyroidism who developed overt and transient hypothyroidism as a consequence of COH. Careful thyroid evaluation is advised for women undergoing COH. (Endocr Pract. 2014;20:e11-e13)     

Virilization of a female infant by a maternal adrenocortical carcinoma

ObjectiveTo describe a possible mechanism underlying the partial virilization of a 46, XX infant by a functional maternal adrenocortical carcinoma (ACC).MethodsWe performed immunocytochemical staining of tumor sections for luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptors. In addition, related reports in the literature are discussed.ResultsA previously healthy mother developed a large cortisoland androgen-producing stage III adrenal tumor that did not interfere with conception or early morphogenesis. The tumor eluded detection until after delivery of a partially virilized 46, XX female infant with ambiguous genitalia. Immunohistochemical staining of tumor sections revealed overexpression of the LH/hCG receptor. Virilization of the genetically female fetus may have resulted from hCG-stimulated steroid secretion by the ACC.ConclusionBecause hypercortisolism and hyperandrogenism are associated with menstrual disturbances and spontaneous abortion, pregnancy in patients with functional adrenal tumors is uncommon. Rarely, maternal steroid excess from a functional adrenal tumor has caused 46, XX disordered sex differentiation. This unusual case demonstrates the influence of hCG on the functionality of an ACC and demonstrates the rare phenomenon of virilization of a female infant by a functional maternal adrenal tumor. (Endocr Pract. 2011;17:e26-e31)