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

Central diabetes insipidus (CDI) is a rare manifestation of acute myeloid leukemia (AML) with unclear etiology. When present, CDI in AML has most often been described in patients with chromosome 3 or 7 aberrations and no abnormalities on brain imaging. In this case, we present a woman with newly diagnosed AML t(12;14)(p12;q13) found to have diabetes insipidus (DI) with partial anterior pituitary dysfunction and abnormal brain imaging. While in hospital, the patient developed an elevated serum sodium of 151 mmol/L with a serum osmolality of 323 mmol/kg and urine osmolality of 154 mmol/kg. On history, she reported polyuria and polydipsia for 5 months preceding hospitalization. Based on her clinical symptoms and biochemistry, she was diagnosed with DI and treated using intravenous desmopressin with good effect; sodium improved to 144 mmol/L with a serum osmolality of 302 mmol/kg and urine osmolality of 501 mmol/kg. An MRI of the brain done for the assessment of neurologic involvement revealed symmetric high-T2 signal within the hypothalamus extending into the mamillary bodies bilaterally, a partially empty sella, and loss of the pituitary bright spot. A pituitary panel was completed which suggested partial anterior pituitary dysfunction. The patient’s robust improvement with low-dose desmopressin therapy along with her imaging findings indicated a central rather than nephrogenic cause for her DI. Given the time course of her presentation with respect to her AML diagnosis, MRI findings, and investigations excluding other causes, her CDI and partial anterior pituitary dysfunction were suspected to be secondary to hypothalamic leukemic infiltration.

Learning points

• Leukemic infiltration of the pituitary gland is a rare cause of central diabetes insipidus (CDI) in patients with acute myeloid leukemia (AML).

• Patients with AML and CDI may compensate for polyuria and prevent hypernatremia with increased water intake.

• AML-associated CDI can require long-term desmopressin treatment, independent of AML response to treatment.

Summary

We present the case of a 23-year-old patient with maturity-onset diabetes of the young type 3 (MODY 3) and premature ovarian insufficiency (POI). There is no known correlation between MODY 3 and POI, although POI can impair glucose metabolism, and MODY can cause microvascular complications such as POI. We did not find literature describing a correlation between these two pathologies nor did we find similar cases described in the literature.

Learning points

• Maturity-onset diabetes of the young type 3 (MODY 3) is an infrequent cause of diabetes that should be considered in young patients with atypical presentation of type 1 or type 2 diabetes.

• MODY 3 can be associated with microvascular complications of diabetes, which is why it is important to diagnose as early as possible.

• Impairment of glucose metabolism has been demonstrated in patients with premature ovarian insufficiency and menopause.

Summary

Mayer–Rokitansky–Kuster–Hauser syndrome is characterized by congenital absence or hypoplasia of the uterus and upper two-thirds of the vagina in both phenotypically and karyotypically normal females with functional ovaries, whereas gonadal dysgenesis is a primary ovarian defect in otherwise normal 46,XX females. An association between these two conditions is extremely rare. We report a 21-year-old female presented with primary amenorrhea and undeveloped secondary sexual characteristics. The karyotype was 46,XX and the hormonal profile revealed hypothyroidism and hypogonadotropic hypogonadism. Pelvic MRI showed class I Mullerian duct anomaly with ovarian dysgenesis. Ultrasound showed bilateral thyroid hypoplasia and brain MRI suggested anterior pituitary hypoplasia. Levothyroxine and hormone replacement therapy were started.

Learning points

• The simultaneous presentation of 46,XX gonadal dysgenesis, Mayer–Rokitansky–Kuster–Hauser syndrome, hypothyroidism, and pituitary hypoplasia is a Possibility.

• Extensive evaluation should be made when a patient presents with one or more of these features.

• The diagnosis imposes a significant psychological burden on patients and adequate counseling should be provided.

• Hormone replacement therapy remains the only therapeutic option for the development of secondary sexual characteristics and the prevention of osteoporosis.

Summary

A 17-year-old lady presented with primary amenorrhoea, headache, nausea and lethargy. She had delayed pubertal development that also includes under-developed breast (Tanner Stage 2). Hormonal investigations showed a high serum prolactin level of 1 680 000 mIU/L (normal value: 45–375 mIU/L), with low oestradiol, progesterone, follicular-stimulating hormone and luteinizing hormone. Early morning cortisol level was 206 nmol/L (normal value: >450 nmol/L), thyroxine was 7.5 pmol/L (normal value: 9.0–24.0 pmol/L) with TSH 5.091 mIU/L (normal value: 0.4–4.5 mlU/L). A pituitary MRI showed a 2.7 (AP) × 3.7 (W) × 4.6 cm (CC) macroadenoma, with invasion into the left cavernous sinus and encasement of cavernous portion of the left internal carotid artery. MRI pelvis showed absent uterus, cervix and 2/3 upper vagina confirming Mullerian hypoplasia. Cytogenetics showed 46XX. These findings were suggestive of Mayer–Rokitansky–Kauser–Hauser (MRKH) syndrome with the presence of a pituitary macroprolactinoma and panhypopituitarism. She was treated with hydrocortisone, levothyroxine and cabergoline. Repeated MRI showed a reduction in tumour size by approximately 50%. This case illustrated a rare coexistence of these two conditions, being only the third reported case in the world. In addition, this would be the first case of a functioning pituitary adenoma in a patient with MRKH syndrome.

Learning points

• Comprehensive hormonal and radiological investigations are important in the management of a young patient with primary amenorrhoea.

• Coexistence pathology of two separate pathologies should be considered in patient presenting with primary amenorrhoea.

• Early diagnosis of MRKH or any disorders of sex development should be treated early, providing pharmacological, surgical, psychological and emotional support to the patient and reducing risk of associated complications.

• Abnormal pituitary hormones, particularly panhypopituitarism, would impose greater impact not only psychologically but also metabolically leading to cardiovascular, morbidity and mortality risks in this patient if not treated early.

• A multidisciplinary approach is necessary for patients presenting with MRKH to ensure appropriate treatments and follow-up across the lifespan of the patient.

Summary

This rare case describes the course of a pregnancy in a patient with a disseminated small intestinal neuroendocrine tumor. The patient received treatment with first-generation somatostatin ligand receptor (SLR) every 4 weeks and had stable disease for several years before her pregnancy. First-generation SLR treatment was initially paused after detection of the pregnancy. During pregnancy, the patient experienced moderate gastro-intestinal discomfort and fatigue, which was considered predominantly pregnancy related. However, since symptoms could be linked to the patient’s cancer, treatment was resumed after the first trimester. Chromogranin-A measurements remained stable throughout pregnancy and was paralleled by the absence of diarrhea and only minor flushing. She gave birth by elective caesarean section in week 37 to a healthy baby. Subsequent follow up imaging immediately after and 10 months postpartum showed no disease progression. The safety profile of SLR treatment during pregnancy in the context of disseminated neuroendocrine tumors (NET) is discussed.

Learning points

• Neuroendocrine neoplasms (NEN) are rare cancers often occurring in the gastro-intestinal tract or lungs.

• Many patients with NEN live for several years with disseminated disease.

• SLR treatment has been given to pregnant patients before; often patients with acromegaly. Pregnancies are reported uneventful.

• This patient completed an uneventful pregnancy while receiving SLR treatment for disseminated neuroendocrine disease and gave birth to a healthy baby.

• More research regarding long term effects and safety signals of SLR treatment during pregnancy are much needed.

Summary

Hypothyroidism occurring in the postpartum period can be due to pituitary or hypothalamic disease as in Sheehan’s syndrome and postpartum autoimmune hypophysitis or due to a primary thyroid disease as in postpartum thyroiditis. It is important that the correct diagnosis is ascertained because hypothalamic or pituitary disorders are often associated with other pituitary hormone deficiencies, especially life-threatening adrenal insufficiency or adrenal crisis. A combination of various symptoms and biochemical markers, especially serum thyroid-stimulating hormone levels dictate the initial diagnostic pathway. We present a case of a woman who presented with a 2-month history of tiredness and neck discomfort following delivery. A thyroid function test demonstrated results, which we initially interpreted as central hypothyroidism. Follow-up results indicated that this was in fact the transition period between the thyrotoxic phase and hypothyroid phases of postpartum thyroiditis. This case highlights the potential for diagnostic confusion between central hypothyroidism and postpartum thyroiditis.

Learning points

• Postpartum thyroiditis affects one in twenty mothers within 12 months of delivery.

• The majority of patients have transient thyrotoxicosis only, some have transient hypothyroidism only, and the rest has a triphasic pattern (thyrotoxic, hypothyroid then a euthyroid phase).

• During the transition from the thyrotoxic phase to hypothyroid phase, when serum TSH is still suppressed, the biochemical results can resemble that of central hypothyroidism.

• If central hypothyroidism is suspected, then urgent diagnostic investigations should be carried out along with the assessment of adrenal function.

• There is a potential for diagnostic confusion between postpartum central hypothyroidism and postpartum thyroiditis; however, the obstetric history, clinical symptoms, and signs (headaches, breastfeeding, goitre, etc.) and serum adrenocorticotropic levels should help with the differential diagnosis.

Summary

Gestational hypertriglyceridemia-induced pancreatitis is associated with significant maternal and fetal morbidity and mortality. We report a case of gestational hypertriglyceridemia-induced pancreatitis in a primigravida at 31-weeks gestation, complicated by impending preterm labor and metabolic acidosis requiring hemodialysis. This was successfully managed with therapeutic plasma exchange (TPE), followed by i.v. insulin, low-fat diet, and omega-3. Triglyceride levels stabilized after TPE and the patient underwent an uncomplicated term delivery. In pregnancy, elevated estrogen and insulin resistance exacerbate hypertriglyceridemia. Management is challenging as risks and benefits of treatment options need to be weighed against fetal wellbeing. We discuss management options including a review of previous case reports detailing TPE use, dietary optimization, and delivery timing. This case emphasizes the importance of multidisciplinary care to optimize maternal and fetal outcomes.

Learning points

• Gestational hypertriglyceridemia-induced pancreatitis has high morbidity.

• A multidisciplinary team approach is a key as maternal and fetal needs must be addressed.

• Rapid lowering of triglycerides is crucial and can be achieved successfully and safely with plasma exchange.

• A low-fat diet while ensuring adequate nutrition in pregnancy is important.

• Timing of delivery requires consideration of fetal maturity and risk of recurrent pancreatitis.

Summary

Adrenocortical carcinoma (ACC) is a malignant disorder with rapid evolution and severe prognosis in adults and most produce cortisol and androgen. Estrogen-secreting adrenocortical carcinomas are extremely rare, especially in women, tend to be larger and have worse prognosis compared with other types of ACCs. We report the case of a 58-year-old woman who presented with bilateral breast enlargement and postmenopausal genital bleeding. She presented high estradiol (818 pg/mL – 25 times above upper normal limit for postmenopausal women) and testosterone (158 ng/dL – 2 times above upper normal limit) levels and no suppression of cortisol after overnight 1 mg dexamethasone test (12.5 µg/dL; normal reference value: < 1.8 µg/dL). The patient had no clinical features of cortisol excess. MRI showed a 12 cm tumor in the right adrenal. Clinical findings of bilateral breast enlargement and postmenopausal genital bleeding with no signs of hypercortisolism associated with hormonal findings of elevated estradiol and testosterone levels would indicate either an ovarian etiology or an adrenal etiology; however, in the context of plasma cortisol levels non-suppressive after dexamethasone test and the confirmation of an adrenal tumor by MRI, the diagnosis of an adrenal tumor with mixed hormonal secretion was made. The patient underwent an open right adrenalectomy and pathological examination revealed an ACC with a Weiss’ score of 6. Estradiol and testosterone levels decreased to normal range soon after surgery. She was put on mitotane treatment as adjuvant therapy, but due to side effects, we were unable to up-titrate the dose and she never achieved serum mitotane dosage above the desired 14 µg/mL. The patient remained in good health without any local recurrence or metastasis until 5 years after surgery, when increased levels of estradiol (81 pg/mL – 2.5 times above upper normal limit) and testosterone (170 ng/dL – 2.1 times above upper normal limit) were detected. MRI revealed a retroperitoneal nodule measuring 1.8 × 1.2 cm. The pathological finding confirmed the recurrence of the estrogen-secreting ACC with a Weiss’ score of 6. After the second procedure, patient achieved normal estrogen and androgen serum levels and since then she has been followed for 3 years. The overall survival was 8 years after the diagnosis. In conclusion, although extremely rare, a diagnosis of an estrogen-secreting ACC should be considered as an etiology in postmenopausal women presenting with bilateral breast enlargement, genital bleeding and increased pure or prevailing estrogen secretion.

Learning points:

• Estrogen-secreting adrenocortical carcinomas are exceedingly rare in adults and account for 1−2% of adrenocortical carcinomas.

• Estrogen-secreting adrenal tumors can be present in females, but are even more rare, we found few cases described in the literature. In women, they present with precocious puberty or postmenopausal bleeding.

• Feminization in the context of an adrenal tumor is considered almost pathognomonic of malignancy. Feminizing ACCs tend to be larger and with worse prognosis compared with nonfeminizing ACCs.

Summary

Struma ovarii is a teratoma of the ovaries predominantly composed of thyroid tissue. Hyperthyroidism associated with struma ovarii is rare, occurring in approximately 8% of cases. Due to the rarity of struma ovarii, available data are limited to case reports and small case series.We report on a 61-year-old female patient with known Hashimoto’s thyroiditis on levothyroxine replacement therapy for years with transition to clinical and biochemical hyperthyroidism despite antithyroid medication with carbimazole (10 mg/day), new diagnosis of urothelial carcinoma and an adnexal mass suspicious of ovarian cancer. The patient underwent resection of the adnexal mass and histopathology revealed a mature teratoma predominantly composed of thyroid tissue showing high levels of sodium iodide symporter protein expression. Following struma ovarii resection and disappearance of autonomous production of thyroid hormones, the patient developed hypothyroidism with severely decreased thyroid hormone levels fT4 and fT3 (fT4 0.4 ng/dL, reference interval 0.9–1.7 and fT3 < 1.0 pg/mL, reference interval 2.0–4.4). This has previously been masked by continued thyroid-stimulating hormone suppression due to long-term hyperthyroidism pre-surgery indicating secondary hypothyroidism, in addition to primary hypothyroidism based on the known co-existing chronic lymphocytic thyroiditis of the orthotopic thyroid gland. Levothyroxine administration was started immediately restoring euthyroidism.This case illustrates possible diagnostic pitfalls in a patient with two concurrent causes of abnormal thyroid function.

Learning points:

• Struma ovarii is an ovarian tumor containing either entirely or predominantly thyroid tissue and accounts for approximately 5% of all ovarian teratomas.

• In rare cases, both benign and malignant struma ovarii can secrete thyroid hormones, causing clinical and biochemical features of hyperthyroidism.

• Biochemical features of patients with struma ovarii and hyperthyroidism are similar to those of patients with primary hyperthyroidism. In such cases, thyroid scintigraphy should reveal low or absent radioiodine uptake in the thyroid gland, but the presence of radioiodine uptake in the pelvis in a whole body radioiodine scintigraphy.

• We give advice on possible diagnostic pitfalls in a case with two simultaneous causes of abnormal thyroid function due to the co-existence of struma ovarii.