Hyperthecosis - Clinical Features, Diagnosis, and Management

What Is Hyperthecosis?

Hyperthecosis or ovarian hyperthecosis is the existence of nests or groups of luteinized theca cells (endocrinal cells that produce androgen substrate required for the synthesis of estrogen) in the ovarian stroma resulting in the excessive presentation of androgen hormone. One of the primary reasons for infertility is the uncontrolled or excessive growth of theca cells. Ovarian hyperthecosis is mainly seen in women during their postmenopausal age. As a result, they present with excessive weight, insulin resistance, virilization (women showing characteristics associated with androgen, a male hormone), and hirsutism (presence of extra facial hair).

What Are the Clinical Features of Hyperthecosis?

• Hyperandrogenism - Patients present with severe hyperandrogenism (excessive level of androgens in the body mainly seen in women than men). The progression of the disorder is slow. The most common symptoms are hirsutism (presence of extra facial hair) and female hair loss. In the case of excess androgen secretion, virilization symptoms (irregular menstrual cycle, acne, and increase in facial hair) are more prominent.

• Overweight and Insulin Resistance - Most women show an increase in weight and resistance to insulin resulting in hyperinsulinemia. As a result, they are more prone to type 2 diabetes and cardiovascular disease. Skin tags (noncancerous skin growth) and acanthosis nigricans (skin condition resulting in thickening and darkening of the skin).

• Hyperplasia of Endometrium and Cancer- Women with ovarian hyperthecosis are more prone to bleeding of the uterus, endometrial carcinoma, and hyperplasia (organ overgrowth due to an increase in cell size) of the endometrium due to excess estrogen in the body.

What Are the Biochemical Findings in Hyperthecosis?

The biochemical findings seen in hyperthecosis are discussed below:

• Serum Total Testosterone Concentrations - It is the most important biochemical marker for confirming hyperandrogenism, a remarkable feature in androgen-secreting tumors and hyperthecosis. For example, if the total serum testosterone in females is less than 150 ng/dl (nanogram per deciliter), it indicates hyperthecosis rather than androgen-secreting tumors where the testosterone concentration is more than 150 ng/dl (nanogram per deciliter).

• Normal or Less Luteinizing Hormone and Follicle-Stimulating Hormone - LH (luteinizing hormone) and FSH (follicle-stimulating hormone) levels are usually low or normal in hyperthecosis however multiple testing is required to confirm as the levels of both these hormones fluctuate during the menopausal period.

• The Normal Level of Serum Androstenedione or Dehydroepiandrosterone Sulfate (DHEAS) - Androstenedione and dehydroepiandrosterone sulfate (DHEAS) are the steroidal hormone responsible for the production of estrogen and testosterone. It is produced by the male (testis) and female (ovary) and the adrenal glands in the body. An elevated level of these hormones is seen in adrenocortical carcinoma.

What Are the Diagnostic Tests for Hyperthecosis?

Various laboratory tests and imaging tests are performed to confirm the diagnosis. If the testosterone level is higher than 150 ng/dl (nanogram per deciliter), imaging tests for the ovaries and adrenal glands are recommended to exclude the possibility of testosterone tumors.

• Initial Laboratory Tests- Hyperandrogenism is seen in many cases, like hyperthecosis, adrenal tumors, and androgen-secreting ovarian tumors. Various biochemical tests are conducted on females who present with hyperandrogenism. These biochemical tests include:

  • Total Serum Testosterone Level Test.

  • Serum Luteinizing and a Follicle - Stimulating Hormone Test.

  • Serum Androstenedione or Dehydroepiandrosterone Sulfate (DHEAS) Test - To exclude adrenocortical carcinoma.

  • Evaluation of Type 2 Diabetes Mellitus- Fasting blood glucose and glycated hemoglobin tests are performed in female patients.

• Ultrasound- Ultrasound of the ovaries and vagina is performed. Ovary size is greater than the normal ovarian size in postmenopausal women. Transvaginal ultrasound presents with bilateral growth of ovarian stroma. Ovaries are more firm and solid with less number of follicles when compared to the ovary of polycystic ovary syndrome (PCOS). Ovary enlargement is seen in women with hyperthecosis, which increases the ovary volume compared to the normal ovary.

• MRI (Magnetic Resonance Imaging)- Magnetic resonance imaging shows overgrowth and refinement of both ovaries.

• CT (Computed Tomography) Scan- It is done to exclude the presence of tumors and cancers in the ovaries and adrenal glands.

• Venous Sampling of Ovary and Adrenal Gland- It is a test done when the diagnostic imaging tests for the adrenal gland and ovary are normal, but the serum testosterone level is high. This test is not done for women who have already attained menopause.

• Gonadotropin-Releasing Hormone (GnRH) Agonist Testing- The test is performed on patients whose biochemical markers and imaging tests suggest hyperthecosis and adrenal tumor, and the testosterone level is more than 150 ng/dl (nanogram per deciliter). Decreased testosterone level after providing a gonadotropin-releasing agonist suggests an ovarian source for the overproduction of androgen.

What Is the Differential Diagnosis for Hyperthecosis?

• Ovarian fibroma.

• Polycystic ovarian syndrome.

• Androgen-secreting adrenal and ovarian tumors.

What Is the Management of Hyperthecosis?

Ovarian hyperthecosis aims to treat hyperandrogenism (symptoms of hirsutism and virilization), excessive weight, insulin resistance, and absence of ovulation (anovulation) in patients. The prime aim of treatment is to stop excess testosterone production in females. Surgical removal of the ovaries is the first choice among doctors to stop testosterone production.

• Bilateral Oophorectomy - Laparoscopic bilateral salpingo-oophorectomy (removal of both the ovaries and the fallopian tubes) is done for females who have already attained menopause. Bilateral oophorectomy treats hyperandrogenism and provides tissue samples to confirm the diagnosis of hyperthecosis by histological examination.

• Gonadotrophin-Releasing Hormone (GnRH) Agonist Therapy - The therapy is a long-term treatment. It is the treatment choice in women where surgical risk is involved due to co-morbidities and in females who are not ready to undergo the removal of ovaries. Surgical removal is the preferred choice if the testosterone levels do not decrease after a long period. Hyperthecosis is a very rare finding in premenopausal women. If diagnosed, GnRH agonist therapy is the first treatment choice.

• Anti-androgen Therapy - It aims to diminish testosterone activities and thus treat the signs of hyperandrogenism like acne, hirsutism (presence of extra facial hair), and hair loss.

• Treatment of Metabolic Disorders (Type 2 Diabetes and Obesity) - Insulin resistance is noted in women suffering from hyperthecosis resulting in type 2 diabetes and excessive weight. Metformin is the first-line therapy to manage blood glucose in such patients. In addition, lifestyle modification needs to be implemented in these patients to reduce their weight and lipid profile (level of low-density lipoproteins).

Conclusion

Hyperthecosis mostly occurs in postmenopausal women and is a rare finding in premenopausal women. Therefore, it is important to check for malignancy of ovary and adrenal tumors if a woman of postmenopausal age presents hyperandrogenism symptoms. Testosterone levels may or may not be significantly elevated; hence, the biochemical markers and imaging techniques play a major role in confirming the diagnosis. Surgical removal of ovaries is a definitive treatment choice; however, based on the patient’s age and associated co-morbidities, gonadotrophin-releasing agonist therapy (GnRH) is also provided to the patients. Despite all these treatment modalities, minor or no improvement is seen in metabolic issues like type 2 diabetes, obesity, and insulin resistance.