Hyperthecosis

PURPOSE: Postmenopausal hyperandrogenism is a rare condition that requires identifying those women bearing a life-threatening tumor. We aimed to study diagnostic work-up and management of postmenopausal androgen excess, proposing an algorithm for clinical decision supporting. METHODS: We conducted an observational cross-sectional study and longitudinal follow-up including 51 consecutive menopausal patients reported for hyperandrogenism between 2003 and 2023 to our clinics...

All girls presenting with virilization (which signifies severe hyperandrogenism) warrant thorough investigation. Ovarian hyperthecosis (OHT) is a rare cause of virilization in premenopausal women. Here, we report the case of a previously healthy 12-year-old Chinese girl with signs of virilization at puberty. Her serum total testosterone was elevated at 5.1 nmol/L (146.97 ng/dL) (normal: <1.4 nmol/L, <40.35 ng/dL). Workup for Cushing syndrome, sex development disorders, congenital adrenal hyperplasia, and adrenal and ovarian androgen-secreting tumors was unrevealing...

We report a case of a 55-year-old postmenopausal woman who presented with symptoms of fatigue, male pattern hair loss, and hirsutism over 3 years. Investigations showed elevated total testosterone levels of 5.0 nmol/L (1.44 ng/mL; range, 0.3-3.1 nmol/L) using Beckman-Unicel-DXI-800 immunoassay. Testosterone levels were repeated by liquid chromatography-tandem mass spectrometry and were found to be elevated at 7.3 nmol/L (2.10 ng/mL). Estradiol was detectable and free androgen index was elevated...

Female androgen excess typically presents with hirsutism, acne, and frontotemporal alopecia. Although the majority of cases are due to underlying polycystic ovary syndrome, non-polycystic ovary syndrome pathology can present a diagnostic and therapeutic challenge. We present 3 cases highlighting the utility of GnRH analogues in diagnosis and treatment of ovarian hyperandrogenism. In case 1, we highlight the role of GnRH analogue testing to localize severe postmenopausal androgen excess, allowing full resolution of symptoms following resection of a benign ovarian steroid-cell tumor...

Hyperandrogenism in women, such as polycystic ovary syndrome, ovarian hyperthecosis, congenital adrenal hyperplasia, and androgen-secreting tumors, are all associated with increased prevalence of cardiovascular risk factors that include type 2 diabetes, hypertension, dyslipidemia, and metabolic syndrome. However, it is not clear whether this also implies enhanced risk of cardiovascular disease and mortality. Furthermore, the involvement of obesity and menopausal status for cardiometabolic risk in these women has not been elucidated...

Hyperandrogenism is an endocrine disorder characterized by an elevated level of androgen in women, which can be due to several etiologies, including ovarian and adrenal causes. Hyperandrogenism can result in hirsutism and virilization in severe cases. Ovarian etiologies can include ovarian hyperthecosis, hilus cell tumors, arrhenoblastomas, and Leydig cell tumors. Diagnosing the specific cause requires comprehensive work, and management is then tailored to address the specific etiology. Treatment may include bilateral oophorectomy and gonadotropin-releasing hormone (GnRH) analogs in combination with antiandrogen therapy...

Special AT-rich sequence-binding protein 2 (SATB2) is a nuclear transcription factor that shows consistent nuclear staining in colorectal adenocarcinoma and osteosarcoma. Following the observation of cytoplasmic staining with this marker in luteinized ovarian stromal cells, we studied the expression of SATB2 in ovarian stromal cells, various types of follicular cysts, and sex cord-stromal tumors. Eighty-five cases were stained for SATB2. Ovarian hilar Leydig cells (n = 12), luteinized stromal cells (n = 10), corpora lutea (n = 4), luteinized follicular cysts (n = 4), and stromal hyperthecosis (n = 6) exhibited consistent, usually diffuse, granular cytoplasmic staining...

Ovarian Leydig cell tumor is a rare type of ovarian steroid cell neoplasms, presenting in only 0.1% of all ovarian tumor cases, and is generally androgen-secreting and unilateral. Although they are often malignant non-spreading tumors, which have excellent prognosis, benign ovarian Leydig cell tumors with low-risk malignancy can be also detected. Ovarian hyperthecosis is a rare non-neoplastic disorder, in most cases bilateral. Ovarian tumors and ovarian hyperthecosis are one of the main causes of hyperandrogenism in postmenopausal women, a condition strongly associated with both hormonal and metabolic changes...

Ovarian stromal hyperthecosis is an uncommon nonneoplastic cause of ovarian hyperandrogenism mainly in postmenopausal women. Here, we present a case of a postmenopausal woman who presented with features of virilization like alopecia and hirsutism. During its workup, two malignancies were diagnosed at a very early stage. Microscopic focus of endometrial adenocarcinoma in a polyp and similar focus of endocervical adenocarcinoma in the subsequent hysterectomy specimen were noted. Presence of synchronous malignancies in the uterus is very rare and it being detected in a patient who presented with a non-related symptom of hairfall makes it an interesting case scenario...

Ovarian hyperthecosis or ovarian stromal hyperplasia is a non-neoplastic functional disorder resulting from the presence of luteinized thecal cells within a hyperplastic ovarian stroma. The condition is more common in postmenopausal women than in those of reproductive age and leads to substantial clinical and laboratory alterations, principally androgenetic alopecia, progressive hirsutism, and elevated testosterone levels. Investigation should include clinical evaluation, laboratory tests, and imaging tests to differentiate between the principal diagnostic hypotheses...

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Postmenopausal hyperandrogenism is a condition caused by relative or absolute androgen excess originating from the ovaries and/or the adrenal glands. Hirsutism, in other words, increased terminal hair growth in androgen-dependent areas of the body, is considered the most effective measure of hyperandrogenism in women. Other symptoms can be acne and androgenic alopecia or the development of virilization, including clitoromegaly. Postmenopausal hyperandrogenism may also be associated with metabolic disorders such as abdominal obesity, insulin resistance, and type 2 diabetes...

Postmenopausal hyperandrogenism is an androgen excess originating from either the adrenals and/or the ovaries. Clinically, symptoms can be moderate (increase in terminal hair growth, acnea) or severe with signs of virilization (alopecia, clitoridomegaly). In either setting, physicians need to exclude relatively rare but potentially life-threatening underlying tumorous causes, such as adrenal androgen-secreting tumors. The objectives of this review are to evaluate which hormonal measurements (T, delta 4 androstenedione, 17 OH progesterone, SDHEA, FSH, LH) and/or imaging (pelvic ultrasound, MRI or adrenal CT-scan) could be useful identifying the origin of the androgen excess...

Hyperandrogenism with virilisation de novo in postmenopausal women is exceedingly rare, with aetiology oscillating between ovarian tumours, adrenal tumours, ovarian hyperthecosis and, less frequently, Cushing's syndrome. We report a case of a postmenopausal woman in her late 60s, referred from her primary healthcare physician to a gynaecology appointment due to hirsutism and vasomotor symptoms. At physical examination, clitoromegaly was also identified. Blood tests revealed severe hyperandrogenemia, with total testosterone above 200 ng/dL, but transvaginal ultrasound and abdominal CT were unremarkable...

Androgen excess in women typically presents clinically with hirsutism, acne or androgenic alopecia. In the vast majority of cases, the underlying aetiology is polycystic ovary syndrome (PCOS), a common chronic condition that affects up to 10% of all women. Identification of women with non-PCOS pathology within large cohorts of patients presenting with androgen excess represents a diagnostic challenge for the endocrinologist, and rare pathology including nonclassic congenital adrenal hyperplasia, severe insulin resistance syndromes, Cushing's disease or androgen-secreting tumours of the ovary or adrenal gland may be missed in the absence of a pragmatic screening approach...

Postmenopausal hyperandrogenism is rare, and without consensus on specific investigative indices, diagnosis is challenging. A 77-year-old woman had a three-year history of hirsutism, male-pattern baldness and increased libido alongside elevated androstenedione, total testosterone and free androgen index levels. A magnetic resonance imaging (MRI) scan showed bilateral ovarian lesions, suggesting ovarian hyperthecosis. Histopathology obtained after a laparoscopic bilateral salpingo-oophorectomy confirmed ovarian hyperthecosis and hilus cell hyperplasia...

Symptoms of hyperandrogenism and virilization in postmenopausal women warrant workup for ovarian hyperthecosis. In this case series, we discuss two patients who presented with symptoms of hyperandrogenism and metabolic abnormalities including insulin resistance stemming from ovarian hyperthecosis. Imaging revealed normal ovaries in both patients. However, both patients had total serum testosterone levels below the lower diagnostic limit for ovarian hyperthecosis. Due to high clinical suspicion of ovarian hyperthecosis, both patients underwent bilateral oophorectomy without venous sampling for ovarian androgens...

Ovarian hyperthecosis (OHT), severe hyperandrogenism after menopause in the absence of ovarian or adrenal tumors, is usually treated by surgical excision. We report a 58-year-old woman presenting with severe hyperandrogenism (serum testosterone 15.7-31.0 nmol/L, normal female <1.8 nmol/L) with menopausal gonadotropins and virilization but no adrenal or ovarian lesions. Multisteroid profiling by liquid chromatography mass spectrometry (LCMS) of adrenal and ovarian vein samples identified strong gradients in the left ovarian vein (10- to 30-fold vs peripheral blood in 17OHP4 , 17 hydroxyprogesterone, 17 hydroxypregnenolone, androstenedione, testosterone, dehydroepiandrosterone) but the right ovarian vein could not be cannulated with the same findings in a second ovarian vein cannulation...

Ovarian cystadenomas may present in a functional manner. Biochemical workup of seemingly benign ovarian lesions should be considered in the appropriate clinical context.

Postmenopausal hyperandrogenism is a state of relative or absolute androgen excess originating from the adrenal glands and/or ovaries clinically manifested by the presence of terminal hair in androgen-dependent areas of the body, and other manifestations of hyperandrogenism such as acne and alopecia or the development of virilization. In such circumstances, physicians must exclude the possibility of rare but serious androgen-producing tumors of the adrenal glands or ovaries. Worsening of undiagnosed hyperandrogenic disorders such as polycystic ovary syndrome, congenital adrenal hyperplasia, ovarian hyperthecosis, Cushing syndrome and iatrogenic hyperandrogenism should be considered for differential diagnosis...