Clinical Overview > Gland/Organ > Ovaries

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Jeremy M W Kirk Department of Endocrinology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK

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Nalin Wickramasuriya Department of Endocrinology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK

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Nicholas J Shaw Department of Endocrinology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK

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Summary

Estrogen is used to induce puberty in peripubertal girls with hypogonadism. Although both synthetic and natural forms are available, along with different routes of administration, in the UK oral ethinyl estradiol and the low-dose oral contraceptive pill are commonly used as hormone replacement therapy for practical reasons. We present five peripubertal girls (aged 12.5–14.9 years) with hypogonadism (two with primary hypogonadism due to Turner syndrome and three with central (secondary) hypogonadism as part of multiple pituitary hormone deficiency) who for a variety of reasons have received milligram doses of estradiol (E2) in error for between 6 weeks and 6 months, instead of the expected microgram doses of ethinyl estradiol. Although there are no direct comparisons in peripubertal girls between synthetic and natural estrogens, all girls had vaginal bleeding whilst receiving the milligram doses and have ended up with reduced final heights, below the 9th centile in 1 and below the 2nd centile in 4. Whilst reduction in final height may be part of the underlying condition (especially in Turner syndrome) the two girls with height predictions performed prior to receiving the estrogen overdose have not achieved their predicted height. Estrogen is one of the few drugs which is available in both milligram and microgram formulations. Clinicians need to be alert to the possibility of patients receiving the wrong formulation and dosage in error.

Learning points

  • Girls with primary and secondary gonadal failure require assistance with pubertal induction.

  • Although several different formulations and route of administration are available, for practical reasons, the majority of girls in the UK receive oral ethinyl estradiol.

  • Estrogen preparations are available in both milligram and microgram formulations, with potential for receiving the wrong dose.

  • Girls receiving milligram rather than microgram preparations all had vaginal bleeding and a short final height.

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Nicole Maison Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany

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Esther Korpershoek Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands

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Graeme Eisenhofer Department of Medicine III, Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany

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Mercedes Robledo Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO) and ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain

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Ronald de Krijger Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
Department of Pathology, Reinier de Graaf Hospital, Delft, The Netherlands

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Felix Beuschlein Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany

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Summary

Pheochromocytomas (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors arising from chromaffin cells of the neural crest. Mutations in the RET-proto-oncogene are associated with sporadic pheochromocytoma, familial or sporadic medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia type 2. In the past, only few cases of pigmented PCCs, PGLs, and one case of pigmented MTC have been reported in the literature. Herein, we present the case of a 77-year old woman with a history of Tako-tsubo-cardiomyopathy and laboratory, as well as radiological, high suspicion of pheochromocytoma, who underwent left-sided adrenalectomy. The 3 cm tumor, which was located on the upper pole of the left adrenal, appeared highly pigmented with dark red to black color. Histologic examinations revealed highly pleomorphic cells with bizarre, huge hyperchromatic nuclei, that immunohistochemically were positive for chromogranin A and synaptophysin, focally positive for HMB45 and negative for melan A. These clinical and pathological features led to the diagnosis of the rare variant of a melanotic ‘black’ pheochromocytoma. In our case a somatic RET mutation in exon 16 (RET c.2753T>C, p.Met918Thy) was detected by targeted next generation sequencing. In summary, this case represents a rare variant of catecholamine-producing tumor with distinct histological features. A potential relationship between the phenotype, the cellular origin and the genetic alterations is discussed.

Learning points

  • Pheochromocytoma is a rare neuroendocrine tumor.

  • Pigmentation is seen in several types of tumors arising from the neural crest. The macroscopic black aspect can mislead to the diagnosis of a metastasis deriving from a malignant melanoma.

  • RET mutation are seen in catecholamine and non-catecholamine producing tumors of the same cellular origin.

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Renata Lange Endocrine Section, Hospital Federal da Lagoa, Rio de Janeiro, Brazil

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Caoê Von Linsingen Endocrine Section, Hospital Federal da Lagoa, Rio de Janeiro, Brazil

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Fernanda Mata Endocrine Section, Hospital Federal da Lagoa, Rio de Janeiro, Brazil

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Aline Barbosa Moraes Department of Internal Medicine and Endocrine Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal de Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 255, 9th Floor, Ilha do Fundão, Rio de Janeiro, 21941-913, Brazil

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Mariana Arruda Department of Internal Medicine and Endocrine Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal de Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 255, 9th Floor, Ilha do Fundão, Rio de Janeiro, 21941-913, Brazil

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Leonardo Vieira Neto Endocrine Section, Hospital Federal da Lagoa, Rio de Janeiro, Brazil
Department of Internal Medicine and Endocrine Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal de Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 255, 9th Floor, Ilha do Fundão, Rio de Janeiro, 21941-913, Brazil

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Summary

Ring chromosomes (RCs) are uncommon cytogenetic findings, and RC11 has only been described in 19 cases in the literature. Endocrine abnormalities associated with RC11 were reported for two of these cases. The clinical features of RC11 can result from an alteration in the structure of the genetic material, ring instability, mosaicism, and various extents of genetic material loss. We herein describe a case of RC11 with clinical features of 11q-syndrome and endocrine abnormalities that have not yet been reported. A 20-year-old female patient had facial dysmorphism, short stature, psychomotor developmental delays, a ventricular septal defect, and thrombocytopenia. Karyotyping demonstrated RC11 (46,XX,r(11)(p15q25)). This patient presented with clinical features that may be related to Jacobsen syndrome, which is caused by partial deletion of the long arm of chromosome 11. Regarding endocrine abnormalities, our patient presented with precocious puberty followed by severe hirsutism, androgenic alopecia, clitoromegaly, and amenorrhea, which were associated with overweight, type 2 diabetes mellitus (T2DM), and hyperinsulinemia; therefore, this case meets the diagnostic criteria for polycystic ovary syndrome. Endocrine abnormalities are rare in patients with RC11, and the association of RC11 with precocious puberty, severe clinical hyperandrogenism, insulin resistance, and T2DM has not been reported previously. We speculate that gene(s) located on chromosome 11 might be involved in the pathogenesis of these conditions. Despite the rarity of RCs, studies to correlate the genes located on the chromosomes with the phenotypes observed could lead to major advances in the understanding and treatment of more prevalent diseases.

Learning points

  • We hypothesize that the endocrine features of precocious puberty, severe clinical hyperandrogenism, insulin resistance, and T2DM might be associated with 11q-syndrome.

  • A karyotype study should be performed in patients with short stature and facial dysmorphism.

  • Early diagnosis and adequate management of these endocrine abnormalities are essential to improve the quality of life of the patient and to prevent other chronic diseases, such as diabetes and its complications.

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W C Candy Sze Department of Endocrinology, St Bartholomew's Hospital, London, EC1A 7BE, UK

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Joe McQuillan Department of Ophthalmology, St Bartholomew's Hospital, London, EC1A 7BE, UK

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P Nicholas Plowman Department of Clinical Oncology, St Bartholomew's Hospital, London, EC1A 7BE, UK

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Niall MacDougall Department of Clinical Oncology, St Bartholomew's Hospital, London, EC1A 7BE, UK

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Philip Blackburn Gamma Knife Unit, St Bartholomew's Hospital, London, EC1A 7BE, UK

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H Ian Sabin Gamma Knife Unit, St Bartholomew's Hospital, London, EC1A 7BE, UK

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Nadeem Ali Department of Ophthalmology, St Bartholomew's Hospital, London, EC1A 7BE, UK

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William M Drake Department of Endocrinology, St Bartholomew's Hospital, London, EC1A 7BE, UK

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Summary

We report three patients who developed symptoms and signs of ocular neuromyotonia (ONM) 3–6 months after receiving gamma knife radiosurgery (GKS) for functioning pituitary tumours. All three patients were complex, requiring multi-modality therapy and all had received prior external irradiation to the sellar region. Although direct causality cannot be attributed, the timing of the development of the symptoms would suggest that the GKS played a contributory role in the development of this rare problem, which we suggest clinicians should be aware of as a potential complication.

Learning points

  • GKS can cause ONM, presenting as intermittent diplopia.

  • ONM can occur quite rapidly after treatment with GKS.

  • Treatment with carbamazepine is effective and improve patient's quality of life.

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Sunita M C De Sousa Department of Endocrinology, St Vincent's Hospital, Sydney, New South Wales, Australia
Hormones and Cancer Group, Garvan Institute of Medical Research, 384 Victoria Street, Sydney, New South Wales, 2010, Australia

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Peter Earls Department of Anatomical Pathology, St Vincent's Hospital, Sydney, New South Wales, Australia

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Ann I McCormack Department of Endocrinology, St Vincent's Hospital, Sydney, New South Wales, Australia
Hormones and Cancer Group, Garvan Institute of Medical Research, 384 Victoria Street, Sydney, New South Wales, 2010, Australia

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Summary

Pituitary hyperplasia (PH) occurs in heterogeneous settings and remains under-recognised. Increased awareness of this condition and its natural history should circumvent unnecessary trans-sphenoidal surgery. We performed an observational case series of patients referred to a single endocrinologist over a 3-year period. Four young women were identified with PH manifesting as diffuse, symmetrical pituitary enlargement near or touching the optic apparatus on MRI. The first woman presented with primary hypothyroidism and likely had thyrotroph hyperplasia given prompt resolution with thyroxine. The second and third women were diagnosed with pathological gonadotroph hyperplasia due to primary gonadal insufficiency, with histopathological confirmation including gonadal-deficiency cells in the third case where surgery could have been avoided. The fourth woman likely had idiopathic PH, though she had concomitant polycystic ovary syndrome which is a debated cause of PH. Patients suspected of PH should undergo comprehensive hormonal, radiological and sometimes ophthalmological evaluation. This is best conducted by a specialised multidisciplinary team with preference for treatment of underlying conditions and close monitoring over surgical intervention.

Learning points

  • Normal pituitary dimensions are influenced by age and gender with the greatest pituitary heights seen in young adults and perimenopausal women.

  • Pituitary enlargement may be seen in the settings of pregnancy, end-organ insufficiency with loss of negative feedback, and excess trophic hormone from the hypothalamus or neuroendocrine tumours.

  • PH may be caused or exacerbated by medications including oestrogen, GNRH analogues and antipsychotics.

  • Management involves identification of cases of idiopathic PH suitable for simple surveillance and reversal of pathological or iatrogenic causes where they exist.

  • Surgery should be avoided in PH as it rarely progresses.

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Siew Hui Foo
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Shahada A H Sobah Department of Haematology, Ampang Hospital, Selangor, Malaysia

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Summary

Hypopituitarism is a rare presentation of Burkitt's lymphoma (BL). The purpose of this report is to present a case of BL presenting with panhypopituitarism and to review other case reports of lymphoma presenting with pituitary dysfunction to highlight the distinguishing features of these cases from other benign aetiologies of pituitary dysfunction such as non-functioning pituitary adenomas. We reviewed a total of 11 cases of lymphoma presenting with pituitary dysfunction published from 1998 to 2013 including the present case. The demographics, clinical presentations, laboratory features, radiological findings, histological diagnosis, treatment administered and outcomes were described. Of the total number of patients, 45.5% of the cases had diffuse large B-cell lymphoma while 27.3% had BL. Anterior pituitary dysfunction was more common than posterior pituitary dysfunction at presentation. The other common associated presenting symptoms were painful ophthalmoplegia, cranial nerve palsies and constitutional symptoms. Hypothalamic–pituitary abnormalities were often demonstrated radiologically to be associated with cavernous sinus and/or stalk involvement. All patients who completed immunochemotherapy responded haematologically. Pituitary dysfunction also improved in most cases although the recovery tended to be partial. In conclusion, a high index of suspicion of underlying malignancy, such as lymphoma, should be present in patients presenting with acute pituitary dysfunction associated with painful ophthalmoplegia, rapidly evolving neurological features, radiological features atypical of a pituitary adenoma and constitutional symptoms. An early diagnosis is essential as prompt initiation of definitive therapy will induce disease remission and recovery of pituitary dysfunction.

Learning points

  • Hypopituitarism may be the presenting symptom of lymphoma in the absence of associated overt symptoms or signs of a haematological malignancy resulting in delay in diagnosis and institution of treatment.

  • Pituitary dysfunction due to tumour infiltration has a greater tendency to involve the posterior pituitary and infundibulum resulting in diabetes insipidus and hyperprolactinaemia compared with a non-functioning pituitary adenoma.

  • The common associated symptoms of hypopituitarism due to lymphoma infiltration of the hypothalamic–pituitary system include painful ophthalmoplegia, cranial nerve palsies and constitutional symptoms.

  • Radiological abnormalities of the hypothalamic–pituitary region are usually present and often associated with cavernous sinus or stalk involvement.

  • With early institution of definitive treatment, both haematological response and improvement of pituitary dysfunction are expected although the reversal of hypopituitarism tends to be partial and delayed.

  • A high index of suspicion of underlying malignancy such as lymphoma should be present in patients presenting with acute pituitary dysfunction associated with painful ophthalmoplegia, radiological features atypical of pituitary adenomas and constitutional symptoms to enable early diagnosis and prompt initiation of definitive therapy.

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Pramila Dharmshaktu Department of Medicine, Maulana Azad Medical College, New Delhi, India

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Aditya Kutiyal Department of Medicine, Maulana Azad Medical College, New Delhi, India

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Dinesh Dhanwal Department of Medicine, Maulana Azad Medical College, New Delhi, India

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Summary

A 21-year-old female patient recently diagnosed with severe hypothyroidism was found to have a large ovarian cyst. In view of the large ovarian cyst, she was advised to undergo elective laparotomy in the gynaecology department. She was further evaluated in our medical out-patient department (OPD), and elective surgery was withheld. She was started on thyroxine replacement therapy, and within a period of 4 months, the size of the cyst regressed significantly, thereby improving the condition of the patient significantly. This case report highlights the rare and often missed association between hypothyroidism and ovarian cysts. Although very rare, profound hypothyroidism that can cause ovarian cysts in an adult should always be kept in the differential diagnosis to avoid unnecessary ovarian surgery.

Learning points

  • Hypothyroidism should be considered in the differential diagnosis of adult females presenting with multicystic ovarian tumours.

  • Adequate thyroid hormone replacement therapy can prevent these patients from undergoing unnecessary and catastrophic ovarian resection.

  • Surgical excision should be considered only when adequate thyroid replacement therapy fails to resolve ovarian enlargement.

  • In younger women with ovarian cysts, it is also desirable to avoid unnecessary surgery so as to not compromise fertility in the future.

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Gautam Das University Hospital of Wales, Cardiff CF14 4XW, UK

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Vinay S Eligar University Hospital of Wales, Cardiff CF14 4XW, UK

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Jyothish Govindan University Hospital of Wales, Cardiff CF14 4XW, UK

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D Aled Rees University Hospital of Wales, Cardiff CF14 4XW, UK

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Summary

Background: Hyperandrogenic states in pregnancy are rare but arise most commonly due to new-onset ovarian pathology in pregnancy. We describe the case of a young woman who presented in the latter half of her pregnancy with features of hyperandrogenism. We review the biochemical and imaging findings and discuss the differential diagnosis.

Case presentation: A 26-year-old woman presented in the later part of her pregnancy with widespread hirsutism. Biochemical testing confirmed hyperandrogenism (testosterone, 13.7 nmol/l and second-trimester pregnancy range, 0.9–4.9 nmol/l), although she had no history of menstrual disturbance, hirsutism or acne prior to conception. Radiological evaluation (ultrasound and magnetic resonance imaging) revealed multiple cystic lesions in both ovaries, leading to a presumptive diagnosis of hyperreactio luteinalis (HL). The implications of maternal hyperandrogenism on foetal virilisation were considered and the patient was counselled appropriately. She delivered a healthy baby boy uneventfully. Androgen levels, hirsutism and acne normalised within a few weeks of delivery.

Conclusion: HL can occur at any stage of pregnancy and is an important differential diagnosis in pregnant patients with features of androgen excess. Most cases regress spontaneously after delivery and major interventions are usually not needed.

Learning points

  • Hyperandrogenism in pregnancy is rare.

  • Clinical features are similar to the non-pregnant state in the mother but virilisation in the foetus can have profound consequences.

  • HL and pregnancy luteoma are the most common ovarian pathologies leading to hyperandrogenism in pregnancy.

  • Spontaneous regression occurs in the post-partum period in the vast majority of cases and surgery is only required for local complications.

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Jayshree Swain Department of Endocrinology, Institute of Medical Sciences, Benaras Hindu University, Varanasi 221005, India

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Shruti Sharma Department of Endocrinology, Institute of Medical Sciences, Benaras Hindu University, Varanasi 221005, India

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Ved Prakash Department of Endocrinology, Institute of Medical Sciences, Benaras Hindu University, Varanasi 221005, India

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N K Agrawal Department of Endocrinology, Institute of Medical Sciences, Benaras Hindu University, Varanasi 221005, India

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S K Singh Department of Endocrinology, Institute of Medical Sciences, Benaras Hindu University, Varanasi 221005, India

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Summary

Ovarian steroid cell tumors are very rare functioning sex-cord stromal tumors. They comprise <0.1% of all ovarian tumors. Previously designated as lipoid cell tumors, one-third of these tumors are considered malignant with the mean age of presentation at around 40 years. We present a case of a 28-year-old female with 2-year history of hirsutism, virilization, and amenorrhea. She was diagnosed with left ovarian tumor, for which she underwent left salpingo-oophorectomy. Histopathology revealed not otherwise specified subtype of steroid cell tumors. The patient resumed menses 2 months after the features of masculinization regressed. Within 1 year of surgery, the patient successfully conceived a full-term baby without any complications. In a young female, the neoplastic etiology of a rapid virilization or menses changing should always be kept in mind. Though commonly observed in adult females, steroid cell tumors have very good surgical outcomes if age at presentation is less and tumor is unilateral, and there are no evidences of bilateral malignancy. Bilateral salpingo-oophorectomy is not required.

Learning points

  • In a case of severe rapid hirsutism and virilization with serum testosterone level more than 200 ng/dl or more than threefold of the normal range, neoplastic conditions should always be suspected.

  • Steroid cell tumor in young women without evidence of malignancy on histopathology has excellent surgical outcomes.

  • Unilateral salpingo-oophorectomy is the surgery of choice.

  • As the frequency of bilateralism is only 6%, prophylactic unaffected side oophorectomy need not be done.

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Roghieh Molaei Langroudi Diagnostic Radiology Department, Poursina Hospital, Guilan University of Medical Sciences, Guilan, Iran

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Fatemeh Ghazanfari Amlashi Guilan Endocrinology and Metabolism Research Center, Razi Hospital, Rasht, Guilan, Iran and

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Mohammad Hassan Hedayati Emami Department of Endocrinology, Guilan Endocrinology and Metabolism Research Center, Razi Hospital, Rasht, Guilan, Iran

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Summary

Background: Spontaneous ovarian hyperstimulation syndrome (sOHSS) can occur following hypothyroidism. Ultrasonography facilitates diagnosis and monitoring of this syndrome. We describe ovarian sonographic changes in a hypothyroid patient with sOHSS after treatment with levothyroxine (l-T4).

Case presentation: A 15-year-old girl presented with abdominal pain and distension for a few months. On examination, she had classical features of hypothyroidism. Abdominal and pelvic ultrasound revealed enlarged ovaries with multiple thin-walled cysts and mild ascitic fluid. On follow-up, abdominal ultrasound showed significant reduction of ovary size after 6 weeks of initiation of l-T4. Normal ovary size with complete regression of ovarian cysts was seen after 4 months.

Conclusion: Serial ultrasound in sOHSS associated with hypothyroidism showed regression of ovarian cysts and ovarian volume after 4 months whereas in other studies, it is reported to happen in various durations, presumably according to its etiology.

Learning points

  • OHSS can rarely occur due to hypothyroidism.

  • This type of OHSS can be simply treated by l-T4 replacement, rather than conservative management or surgery in severe cases.

  • Ultrasound follow-up shows significant regression of ovarian size and cysts within 6 weeks of initiation of l-T4.

  • Ultrasound follow-up shows normal ovarian size with complete resolution of ovarian cysts 4 months after treatment.

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