Summary

Ovarian hyperstimulation syndrome (OHSS) usually occurs in patients undergoing assisted reproduction techniques and ovulation induction. Its variant, spontaneous ovarian hyperstimulation syndrome, a potentially life-threatening disorder, is uncommon and only a few cases have been reported in association with hypothyroidism. This study analysed five patients with untreated chronic hypothyroidism presenting with multicystic ovaries, isosexual precocious puberty, and delayed bone age; subsequently, the follow-up and regression of ovarian pathology was assessed. Two patients had presented to the emergency department with menorrhagia and hypotension, of these, one had ovarian torsion at presentation. Three patients presented to the outpatient department: one for evaluation of short stature, one for premature menarche, and another with polycystic ovaries. They were all diagnosed with long-standing, untreated chronic hypothyroidism. There was regression of the size of the cystic ovaries on subsequent follow-up. In all these patients, long-standing hypothyroidism had resulted in ovarian hyperstimulation syndrome. The potentially life-threatening complications of this syndrome may be prevented by careful screening and a strong index of clinical suspicion at the outset.

Learning points

• Long-standing, untreated primary hypothyroidism may result in spontaneous ovarian hyperstimulation syndrome.

• A high index of suspicion is required for an early and accurate diagnosis.

• The requirement for interdepartmental collaboration between gynaecology and endocrinology departments is essential for the successful management of this life-threatening but easily treatable disorder.

Summary

At the end of the 19th century, an 18-year-old lady gave birth to a well-proportioned, though very small, son. After delivery, the mother developed a full-grown beard, whereas the son always remained of small stature. The mother developed diabetes mellitus and died, aged 59, from a complicated severe cold. The son died at the age of 91 because of chronic kidney disease. The differential diagnosis in the son is isolated growth hormone deficiency. The mother might have suffered luteoma of pregnancy, polycystic ovary syndrome (PCOS), or Sertoli–Leydig cell tumor(s). The two cases are apparently coincidental/not related in pathophysiology.

Learning points

• Hirsutism occurring directly postpartum can have several causes.

• Patients with isolated growth hormone deficiency can live a long life without the substitution of growth hormone.

• Coincidence does not necessarily imply correlation.

• In the past, patients with endocrine disorders like severe hirsutism or small stature were employed at circuses and fairs to entertain the audience as curiosities.

Summary

A 6.6-year-old female presented to endocrinology with precocious puberty for evaluation and management. Workup was initiated, and a diagnosis of central precocious puberty was confirmed. A decision was made to initiate pubertal blockade using gonadotropin-releasing hormone agonist (GnRHa) therapy with depot leuprolide acetate injections every 3 months. The patient received the first depot leuprolide acetate injection in the right ventrogluteal area. Six hours following the injection, the patient was reported to be inconsolable in pain, which was localized to the right hip site of the earlier injection and associated with a refusal to ambulate. The pain and discomfort continued to progress over the next 24 h despite an alternating regimen of Tylenol and ibuprofen prompting admission to the emergency department. Vital signs demonstrated a low-grade fever and elevated C-reactive protein. An ultrasound of the right hip demonstrated fluid accumulation within the joint. Over the next week, the patient was unable to walk independently and required assistance for activities of daily living. By 2 weeks after the injection, the pain began to remit, and the patient resumed activities of daily living. Following consultation with allergy, a decision was made to continue GnRHa suppressive therapy with an alternative analog (Triptodur). The patient tolerated subsequent treatment without reaction.

Learning points

• Although gonadotropin-releasing hormone agonists (GnRHa) have a generally good safety profile, there is a history of both local and systemic hypersensitivity reactions associated with their use.

• Despite the long-acting formulation of depot leuprolide acetate, the systemic reaction in this case appears to be self-limited.

• Discontinuation of therapy or a change to an alternative formulation of GnRHa analog should be considered based on the need for therapy versus the potential risk of rechallenge.

Summary

Total testosterone, which is peripherally converted to its biologically active form dihydrotestosterone (DHT), is the first-line hormone investigation in hyperandrogenic states and infertility in premenopausal women. Polycystic ovary syndrome (PCOS), the most common cause of hyperandrogenism and infertility in young women, is often associated with mild elevations of total testosterone. Whereas very high levels of total testosterone (>2–3 SD of normal reference), are most often associated with hyperandrogenic signs, menstrual irregularity, rapid onset of virilization, and demand a prompt investigation. Herein, we report a case of a 32-year-old woman who was referred to the endocrinology outpatient clinic due to secondary amenorrhea and extremely high testosterone levels without any virilization signs. We initially suspected pitfalls in the testosterone laboratory test. Total serum testosterone decreased after a diethyl-ether extraction procedure was done prior to the immunoassay, but testosterone levels were still elevated. An ovarian steroid-cell tumor (SCT) was then revealed, which was thereby resected. Twenty-four hours post surgery, the total testosterone level returned to normal, and a month later menstruation resumed. This case emphasizes that any discrepancy between laboratory tests and the clinical scenario deserves a rigorous evaluation to minimize misinterpretation and errors in diagnosis and therapeutic approach. Additionally, we describe a possible mechanism of disease: a selective peripheral target-tissue response to high testosterone levels that did not cause virilization but did suppress ovulation and menstruation.

Learning points

• Total testosterone is the most clinically relevant hormone in investigating hyperandrogenic states and infertility in premenopausal women.

• Very high total testosterone levels in women (>2–3 SD of normal reference) are most often associated with hyperandrogenic signs, menstrual irregularities, and a rapid onset of virilization.

• In women with very elevated testosterone levels and the absence of clinical manifestations, laboratory interference should be suspected, and diethyl ether extraction is a useful technique when other methods fail to detect it.

• Ovarian steroid cell tumors (SCT) encompass a rare subgroup of sex cord-stromal tumors and usually secrete androgen hormones. SCTs are clinically malignant in 25–43% of cases.

• A selective response of peripheral target tissues to testosterone levels, with clinical manifestations in some tissues and no expression in others, may reflect differences in the conformation of tumor-produced testosterone molecules.

Summary

Struma ovarii is an ovarian teratoma that comprises 2–5% of all ovarian teratomas. Malignant transformation of struma ovarii occurs in less than 5% of all cases, and metastatic disease is even rarer. We report two cases initially diagnosed with benign struma ovarii that presented malignant transformation, specifically highly differentiated follicular carcinoma of the ovary (HDFCO), some years after the first diagnosis. Case 1 concerns a 37-year-old female featuring HDFCO of the right ovary with multiple metastatic foci, who was diagnosed with benign struma ovarii 14 years ago. Case 2 concerns a 26-year-old female diagnosed with HDFCO of the left ovary. This patient was initially diagnosed with benign struma ovarii 6 years ago that recurred 4 years after the diagnosis. Both patients were treated with surgery, adjunctive total thyroidectomy, and radioactive iodine (¹³¹I) therapy.

Learning points

• Malignant transformation of struma ovarii is very rare (<5%).

• Diagnosis of HDFCO without extra ovarian dissemination is difficult due to the resemblance of its histological appearance with normal thyroid tissue.

• There is no consensus on the postoperative treatment of malignant struma ovarii (MSO). Clinical and histological features of MSO should be assessed for the postoperative treatment decisions.

• TSH suppression and thyroglobulin level measurements are necessary for patient follow-up.

Summary

We report a case of catamenial erythema multiforme major in a 46-year-old female. She was treated successfully with goserelin, a GnRH agonist, until the expected age of menopause; however, its therapeutic effects persisted for longer than expected, possibly due to accumulation in adipose tissue.

Learning points

• A group of menstrual cycle-related dermatoses and hypersensitivity syndromes exist but are rarely reported in the literature.

• A history of recurrent cutaneous eruptions in premenopausal females should be considered in the context of the menstrual cycle.

• The diagnosis of menstrual cycle-related dermatoses is largely clinical, although provocation testing can assist.

• Treatment options are broad and are aimed at reducing the immune response and/or suppressing ovulation.

• Goserelin may accumulate and have a gonadotrophin-suppressing effect for longer than expected.

Summary

Severe Cushing’s syndrome from an ectopic adrenocorticotropic hormone-producing tumour is rare but often demands rapid diagnostics and treatment of hypercortisolism with its comorbidities. Pharmacotherapy of hypercortisolism by ketoconazole, metyrapone and osilodrostat is currently available. If unsuccessful or insufficient a bilateral adrenalectomy is an option. We present a 28-year-old female with severe Cushing’s syndrome caused by a bronchial metastatic neuroendocrine tumour (NET). Hypercortisolism was efficiently treated by osilodrostat with block–replace and then titration regimen. A once-daily dose was finally used with normalised cortisol levels. Androgen levels measured by liquid chromatography–mass spectrometry were slightly elevated during the treatment but without any symptoms. A simple once-daily use of osilodrostat with titration regimen led to normalised cortisol levels in a severe Cushing’s syndrome patient with an uncurable bronchial NET. Transient hypocortisolism during treatment appeared but was easily treated by hydrocortisone.

Learning points

• Cushing’s syndrome from an ectopic adrenocorticotropic hormone-producing tumour is rare.

• Cortisol upregulation is often severe and rapid, though clinical signs are not always fully pronounced.

• Rapid treatment is a key for preventing and reducing complications such as fractures, thromboembolism, bleeding, hyperglycaemia, and arterial hypertension.

• The novel potent steroidogenesis inhibitor osilodrostat can be used as first-line treatment for reducing hypercortisolism.

Summary

Endometrioid carcinomas of the ovary are a subtype of epithelial ovarian tumors, with sertoliform endometrioid carcinomas being a rare variant. We report a case of a previously healthy premenopausal woman presenting with androgenic symptoms in the form of hirsutism and male pattern alopecia. On further testing, she was found to have high levels of luteinizing hormone and total testosterone levels, and imaging revealed a large pelvic abdominal mass in the right ovary. She underwent total hysterectomy with bilateral salpingo-oophorectomy. Microscopy and histopathology confirmed the diagnosis of sertoliform endometrioid carcinoma. Her symptoms improved significantly on follow-up. Androgenic tumors might not be common in premenopausal women; however, it is important to maintain a high level of suspicion in patients presenting with virilizing symptoms especially of rapid progression.

Learning points

• Our 47-year-old patient presented with virilizing symptoms that were rapidly progressing, which raises the suspicion of an underlying androgen secreting neoplasm.

• Sertoliform endometrioid carcinoma (SEC) is an extremely rare variant of endometrioid carcinomas and tend to present at an earlier stage as compared to most endometrioid carcinomas of the ovary.

• Recognition of SEC in virilizing patients is important as it is a well-differentiated, low-grade malignancy with a good prognosis when confined to the ovary.

Summary

A 33-year-old female presented in 2013 with left flank pain. Ultrasound and MRI pelvis showed a complex mass 9 × 7 cm arising from the left ovary suggestive of ovarian torsion. She underwent a laparoscopic cystectomy, but the patient was lost to follow-up. Three years later, she presented with abdominal distension. Ultrasound and CT scan revealed a solid left ovarian mass with ascites and multiple peritoneal metastasis. Investigations showed elevated CA 125, CA 19-9. Ovarian malignancy was suspected. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy on November 2016. The histopathology confirmed a well-differentiated thyroid cancer of ovarian origin with features of a papillary follicular variant without evidence of ovarian cancer and the thyroglobulin (Tg) level was elevated, more than 400 consistent with the diagnosis of malignant struma ovarii. The follow-up post-surgery showed normalization of CA 125, CA 19-9 and Tg. The patient underwent total thyroidectomy on January 2017. The histology was benign excluding thyroid cancer metastases to the ovary. She was started on thyroxine suppression, following which she received two ablation doses ¹³¹iodine (¹³¹I) each 5.3 GBq. The Tg remains slightly elevated at less than 10. ¹³¹I WBS showed no residual neck uptake and no distant avid metastasis. She was planned for molecular analysis which may indicate disease severity. We describe a case of malignant struma ovarii with widespread metastatic dissemination and a good response to surgery and ¹³¹I treatment without recurrence after 5 years of follow-up. The Tg remains slightly elevated indicating minimal stable residual disease.

Learning points

• Malignant struma ovarii is a rare disease; diagnosis is difficult and management is not well defined.

• Presentation may mimic advanced carcinoma of the ovary.

• Predominant sites of metastasis are adjacent pelvic structures.

• Thyroidectomy and ¹³¹iodine therapy should be considered. The management should be similar to that of metastatic thyroid cancer.

Summary

The coexistence of neurofibromatosis type 1 (NFT1) and Turner syndrome (TS) has only been reported in a few patients and may represent a diagnostic challenge. We describe the case of a 16-year-old girl, with a prior clinical diagnosis of NFT1, who was referred to Endocrinology appointments for the etiological study of primary amenorrhea. Evaluation of the anterior pituitary function was requested and hypergonadotropic hypogonadism was detected. During the etiological study, a 45X karyotype was found and TS was diagnosed. The fact that NFT1 can also be associated with short stature, short broad neck and hypertelorism was likely responsible for TS being diagnosed in late adolescence. As both TS and NFT1 are relatively common genetic disorders, it is important to be alert to the possibility that the presence of one disease does not invalidate the other.

Learning points

• The concomitant presence of two syndromes in the same patient is unlikely and represents a diagnostic challenge.

• Some phenotypic characteristics and clinical manifestations may be shared by several syndromes.

• Some syndromes, such as neurofibromatosis type 1 may have very heterogeneous presentations.

• It is important to be alert to the characteristics that are not explained by the initial diagnosis.

• If such features are present, diagnostic work-up must be performed regardless of the initial syndromic diagnosis.