Summary

We report a case of a woman with a diagnosis of breast cancer who unintentionally started gaining weight, feeling tired, and constipated 44 weeks after the initiation of trastuzumab. Hypothyroidism secondary to an autoimmune thyroiditis associated with trastuzumab was diagnosed, the first case described in Portugal and the fourth case described worldwide. Our intention regarding the publication of this case report is to alert the clinicians treating people with trastuzumab that they should ask the patients about symptoms of hypothyroidism and should screen the thyroid function of the patients before, during, and after the initiation of trastuzumab.

Learning points

• Trastuzumab is a humanized MAB used in HER2-positive breast and gastric cancer.

• Trastuzumab-associated autoimmune thyroid disease (AITD) is rare (incidence rate in an RCT of 0.3%).

• Manifestations of autoimmune thyroiditis associated with trastuzumab resemble those of hypothyroidism in other clinical contexts, but the presence of goiter is highlighted as a reason for medical evaluation. Biochemically, it is characterized by an increased thyroid-stimulating hormone (TSH) with or without a low FT4/FT3, and sonographically with a pattern of thyroiditis.

• The treatment consists of levothyroxine, in a dose of 1.6–1.8 µg/kg/day, with re-evaluation of the thyroid function in 4–6 weeks.

• We report the first case of autoimmune thyroiditis secondary to trastuzumab in Portugal.

• It is important to evaluate the thyroid function before, during, and after the initiation of this therapeutic agent.

Summary

Cushing’s syndrome due to ectopic adrenocorticotropic hormone (ACTH) secretion (EAS) by a pheochromocytoma is a challenging condition. A woman with hypertension and an anamnestic report of a ‘non-secreting’ left adrenal mass developed uncontrolled blood pressure (BP), hyperglycaemia and severe hypokalaemia. ACTH-dependent severe hypercortisolism was ascertained in the absence of Cushingoid features, and a psycho-organic syndrome developed. Brain imaging revealed a splenial lesion of the corpus callosum and a pituitary microadenoma. The adrenal mass displayed high uptake on both ¹⁸F-FDG PET/CT and ⁶⁸Ga-DOTATOC PET/CT; urinary metanephrine levels were greatly increased. The combination of antihypertensive drugs, high-dose potassium infusion, insulin and steroidogenesis inhibitor normalized BP, metabolic parameters and cortisol levels; laparoscopic left adrenalectomy under intravenous hydrocortisone infusion was performed. On combined histology and immunohistochemistry, an ACTH-secreting pheochromocytoma was diagnosed. The patient's clinical condition improved and remission of both hypercortisolism and catecholamine hypersecretion ensued. Brain magnetic resonance imaging showed a reduction of the splenial lesion. Off-therapy BP and metabolic parameters remained normal. The patient was discharged on cortisone replacement therapy for post-surgical hypocortisolism. EAS due to pheochromocytoma displays multifaceted clinical features and requires prompt diagnosis and multidisciplinary management in order to overcome the related severe clinical derangements.

Learning points

• A small but significant number of cases of adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome are caused by ectopic ACTH secretion by neuroendocrine tumours, which is usually associated with severe hypercortisolism causing severe clinical and metabolic derangements.

• Ectopic ACTH secretion by a pheochromocytoma is exceedingly rare but can be life-threatening, owing to the simultaneous excess of both cortisol and catecholamines.

• The combination of biochemical and hormonal testing and imaging procedures is mandatory for the diagnosis of ectopic ACTH secretion, and in the presence of an adrenal mass, the possibility of an ACTH-secreting pheochromocytoma should be taken into account.

• Immediate-acting steroidogenesis inhibitors are required for the treatment of hypercortisolism, and catecholamine excess should also be appropriately managed before surgical removal of the tumour.

• A multidisciplinary approach is required for the treatment of this challenging entity.

Summary

A patient treated with intramuscular testosterone replacement therapy for primary hypogonadism developed blurred vision shortly after receiving his testosterone injection. The symptom resolved over subsequent weeks and recurred after his next injection. A diagnosis of central serous chorioretinopathy (CSR) was confirmed following ophthalmology review. A decision was made to change the patient’s testosterone regime from this 12-weekly intramuscular injection to a daily topical testosterone gel, given the possibility that peak blood levels of testosterone following intramuscular injection were causing his ocular complaint. His CSR did not recur after this change in treatment. CSR secondary to testosterone therapy is a rare finding but has been reported previously in the literature.

Learning Points

• Blurred vision in patients treated with testosterone replacement therapy (TRT) should prompt an ophthalmology review.

• The potential for reduced risk of central serous chorioretinopathy (CSR) with daily transdermal testosterone remains a matter of conjecture.

• CSR is a rare potential side effect of TRT.

Learning points

• Ectopic Cushing's syndrome (ECS) accounts for 15% of endogenous Cushing's syndromes. Its infrequency implies that both diagnosis and treatment can be a challenge for clinicians without experience in its management.

• The most common location is the lung. Although older series reported small cell lung carcinoma (SCLC) as the main ECS-producing tumour, currently most cases are attributed to lung carcinoids.

• Low-grade tumours (lung carcinoids) present themselves with a more subtle and gradual hypercortisolism, and clinically this can be difficult to differentiate from hypercortisolism due to CD. In contrast, high-grade tumours (SCLC) show severe hypercortisolism with rapid evolution.

• The diagnostic approach is complex especially when the tumour is not previously known and the clinical presentation is subtle. Functional tests are mandatory in these cases, and nuclear medicine imaging can help when conventional imaging tests fail to identify the tumour.

• ECS treatment includes a wide variety of modalities oriented to treat both the excess of cortisol and the tumour itself. The tumour prognosis depends fundamentally on the type of adrenocorticotropic hormone-secreting tumour.

• Expert and multidisciplinary team is essential for successfully treating these complex and ill patients.

Summary

Primary hyperparathyroidism (PHPT) is a common endocrinological pathology; nonetheless, it is rarely diagnosed in pregnancy. Primary hyperparathyroidism can present with clinically expressed hypercalcemia. High Ca levels in the blood may lead to a miscarriage. We present the case of a 39-year-old woman who visited our Endocrinology clinic in search of a cause of infertility. Blood work showed elevated Ca and parathyroid hormone (PTH) levels. Upper left parathyroid gland adenoma was found during a neck ultrasound. Parathyroid gland adenoma was likely the cause of PHPT and was treated with parathyroidectomy. Surgery was carried out, and the upper left parathyroid lobe adenoma was removed. High levels of Ca were found in all performed blood works since the first visit to the clinic, but following the surgery, Ca levels of the patient were in the normal range and the woman got pregnant for the third time, later delivering a healthy baby. In conclusion, we would like to put forward the idea that an evaluation of Ca level in the blood should be included in the protocol for treating patients with recurrent miscarriages. Early detection of hypercalcemia can improve the outcomes of disease that primary hyperparathyroidism can cause. Swift and accurate decrease of serum Ca correspondingly safeguards the woman from a possible pregnancy loss along with complications that arise from it.–

Learning points

• Primary hyperparathyroidism (PHPT) is a common endocrinological pathology, nonetheless, it is rarely diagnosed in pregnancy.

• Primary hyperparathyroidism can present with clinically expressed hypercalcemia, and high Ca levels in the blood may lead to a miscarriage.

• Early detection of hypercalcemia can improve the outcomes of disease that primary hyperparathyroidism can cause.

• Swift and accurate decrease of serum Ca correspondingly safeguards the woman from a possible pregnancy loss along with complications that arise from it.

• All pregnant patients with hypercalcemia should be assessed for the presence of primary hyperparathyroidism as it is likely the cause.

Summary

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive inherited syndrome caused by mutations in autoimmune regulator (AIRE) gene. The three clinical components of this syndrome are mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. In addition to these frequent symptoms, many other components have been reported including gastrointestinal manifestations.We report a case of a 17-year-old Caucasian female patient diagnosed with APECED who presented with acute abdominal pain. Her medical history revealed chronic digestive discomfort without bowel movement disorders. The patient needed a significant increase in doses of calcium supplementation and hydrocortisone which appeared to be partially inefficient. Investigation with esophagogastroduodenoscopy and biopsy showed autoimmune atrophic gastritis. The patient eventually needed increasing doses of treatment received in order to achieve desired clinical and biological therapeutic goals.

Learning points

• Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive inherited syndrome caused by mutations in the autoimmune regulator (AIRE) gene.

• The three clinical components of this syndrome that appear in early childhood are mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency.

• In addition to these frequent symptoms, many other components have been reported including gastrointestinal manifestations like atrophic gastritis. They can be caused by many abnormalities including atrophic gastritis and the modification of intestinal biofilm and microbiota.

• Early diagnosis and treatment of gastrointestinal manifestations associated with APECED prevent multiple life-threatening consequences like acute adrenal crisis and severe symptomatic hypocalcemia.

Summary

We report the successful delivery of a healthy baby after intracytoplasmic sperm injection (ICSI) with frozen-thawed autologous sperm, cryostored for 26 years, the longest successful autologous sperm cryostorage reported. Sperm was cryostored for a 15-year-old boy at the time of his cancer diagnosis. Semen samples were frozen with cryoprotectant, using a graduated vapour-phase nitrogen protocol. Straws were stored in a large vapour-phase nitrogen tank until transfer for use. The couple underwent a single ICSI–in vitro fertilisation procedure using the frozen-thawed sperm with a transfer of five fertilised embryos, resulting in the live birth of a healthy baby boy. This reinforces the importance of offering sperm cryopreservation to men who have not completed their family prior to gonadotoxic treatment for cancer or other diseases. As practical, low-cost fertility insurance, it should be offered to any young man who can collect semen and it provides essentially unlimited duration of fertility preservation.

Learning points

• Gonadotoxic chemo or radiotherapy treatment for cancer or other diseases usually causes temporary or permanent male infertility.

• Sperm cryostorage serves as a practical, low-cost insurance to facilitate future paternity.

• All men who have not completed their families and are scheduled for gonadotoxic treatments should be offered sperm cryostorage.

• There is no lower age limit for young men who can collect semen.

• Sperm cryostorage offers essentially indefinite duration for the preservation of male fertility.

Summary

Paraneoplastic syndromes (PS) are uncommon and are known to mimic other clinical entities, often carrying significant morbidity and mortality. The commonest cause of extra-ocular muscle enlargement (EOME) is thyroid eye disease (TED). Rarely, PS can cause EOME and masquerade as TED. We describe a 52-year-old female who presented with diarrhoea, acute kidney injury and electrolyte imbalance. An ophthalmic review identified right upper lid retraction. MRI orbits showed increased thickness of the inferior and medial recti bilaterally, presumed as TED. Whilst investigating her diarrhoea, imaging revealed a large rectosigmoid tumour which required surgical excision. In the context of electrolyte disturbance and acute kidney injury, a diagnosis of McKittrick–Wheelock syndrome (MWS) was made. Following successful surgery, electrolyte imbalance, diarrhoea and eyelid retraction improved. Repeat MRI orbits displayed complete resolution of EOME. To our knowledge, this is the first case of MWS presenting with PS-EOME masquerading as TED.

Learning points

• McKittrick–Wheelock syndrome (MWS) is a rare disorder, although likely under-recognised, which is characterised by diarrhoea, dehydration and electrolyte depletion that results from a hypersecretory colorectal neoplasm.

• Definitive treatment of MWS involves the resection of the colorectal neoplasm.

• Bilateral ophthalmopathy that appears to be Graves’ ophthalmopathy on imaging, though clinical and biochemical evidence fails to identify a thyroid pathology, has been associated with malignancy on rare occasions. Such patients should be investigated for potential malignant causes of their ophthalmopathy.

Summary

A 31-year-old woman with complete androgen insensitivity syndrome (CAIS) experienced breast volume fluctuations during biphasic hormone replacement therapy consisting of estradiol and cyclical dydrogesterone, a progestin. 3D breast volume measurements showed a 100 cc volume (17%) difference between estradiol monotherapy and combined estradiol and dydrogesterone treatment. Progestogen-dependent breast volume changes have not been reported in the literature. Our findings suggest a correlation between progestogen use and breast volume. Due to the rapid cyclical changes, we hypothesize that the effect is caused by fluid retention.

Learning points

• There is limited reports available on the effects of progesterone on breast development and volume.

• 3D imaging provides an easy-to-use method to quantify breast volume.

• The patient in our case description clearly showed that cyclic progesterone use might induce substantial cyclic changes in breast volume.

• In women with complete androgen insensitivity syndrome (CAIS), monotherapy with estrogen or continuous supplementation of progesterone might be preferable over cyclic progesterone use.

Summary

We report a rare case of biopsy-proven isolated immunoglobulin G4 (IgG4)-related hypophysitis and Rathke’s cleft cyst (RCC) presenting as panhypopituitarism. A 54-year-old Caucasian female presented with symptoms of slurred speech, altered mental status, polyuria and polydipsia and was found to have panhypopituitarism. Brain MRI showed a suprasellar mass with suspected intralesional hemorrhage. She underwent trans-sphenoidal resection due to MRI evidence of compression of the optic chiasm and left optic nerve. Preoperatively, she was started on hydrocortisone, levothyroxine and desmopressin. Histopathology demonstrated a RCC with adjacent lymphoplasmacytic hypophysitis with numerous IgG4-immunoreactive plasma cells. Hydrocortisone was stopped at 10 months after confirming hypothalamic-pituitary-adrenal (HPA)-axis recovery and desmopressin was stopped at 1 year. There was recurrence of a cystic mass at 1 year follow-up. Over 4 years of follow-up, she continued to require levothyroxine, and the mass remained stable in size. In order to begin to understand how this case’s unique histopathological presentation influences clinical presentation, pituitary imaging and prognosis, we present an accompanying literature review.

Learning points

• Isolated IgG4 hypophysitis and coexisting Rathke’s cleft cyst is a rare condition, which presents a diagnostic challenge.

• Recognizing its characteristic features can assist with early recognition and initiation of therapy to promote optimal outcomes.

• Further studies investigating the mechanisms promoting co-occurrence of these entities and their effect on prognosis are needed.