Severe hyponatremia and osmotic demyelination syndrome (ODS) are opposite ends of a spectrum of emergency disorders related to sodium concentrations. Management of severe hyponatremia is challenging because of the difficulty in balancing the risk of overcorrection leading to ODS as well as under-correction causing cerebral oedema, particularly in a patient with chronic hypocortisolism and hypothyroidism. We report a case of a patient with Noonan syndrome and untreated anterior hypopituitarism who presented with symptomatic hyponatremia and developed transient ODS.
Patients with severe anterior hypopituitarism with severe hyponatremia are susceptible to the rapid rise of sodium level with a small amount of fluid and hydrocortisone.
These patients with chronic anterior hypopituitarism are at high risk of developing ODS and therefore, care should be taken to avoid a rise of more than 4–6 mmol/L per day.
Early recognition and rescue desmopressin and i.v. dextrose 5% fluids to reduce serum sodium concentration may be helpful in treating acute ODS.
Ectopic ACTH-secreting pulmonary neuroendocrine tumors are rare and account for less than 5% of endogenous Cushing’s syndrome cases. We describe an unusual case of metastatic bronchial carcinoid tumor in a young woman presenting with unprovoked pulmonary emboli, which initially prevented the detection of the primary tumor on imaging. The source of ectopic ACTH was ultimately localized by a Gallium-DOTATATE scan, which demonstrated increased tracer uptake in a right middle lobe lung nodule and multiple liver nodules. The histological diagnosis was established based on a core biopsy of a hepatic lesion and the patient was started on a glucocorticoid receptor antagonist and a somatostatin analog. This case illustrates that hypercogulability can further aggravate the diagnostic challenges in ectopic ACTH syndrome. We discuss the literature on the current diagnosis and management strategies for ectopic ACTH syndrome.
In a young patient with concurrent hypokalemia and uncontrolled hypertension on multiple antihypertensive agents, secondary causes of hypertension should be evaluated.
Patients with Cushing’s syndrome can develop an acquired hypercoagulable state leading to spontaneous and postoperative venous thromboembolism.
Pulmonary emboli may complicate the imaging of the bronchial carcinoid tumor in ectopic ACTH syndrome.
Imaging with Gallium-68 DOTATATE PET/CT scan has the highest sensitivity and specificity in detecting ectopic ACTH-secreting tumors.
A combination of various noninvasive biochemical tests can enhance the diagnostic accuracy in differentiating Cushing’s disease from ectopic ACTH syndrome provided they have concordant results. Bilateral inferior petrosal sinus sampling remains the gold standard.
Ellena CottonFaculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, UK Specialist Medicine, Manchester University Foundation Trust, Manchester, UK
A young woman carrying germline DICER1 mutation was discovered to have a pituitary microprolactinoma when she became amenorrhoic. The mutation was identified as a result of family screening following the early death of the patient’s daughter with ovarian cancer. The patient was in follow-up screening for thyroid disease, and investigations were initiated when she became amenorrhoic. MR scan revealed a 6 mm diameter pituitary microadenoma and raised prolactin. The prolactin was efficiently suppressed with low-dose cabergoline, and her menstrual cycles resumed. Dicer is an RNase enzyme, which is essential for processing small non-coding RNAs. These molecules play pleiotropic roles in regulating gene expression, by targeting mRNA sequences for degradation. DICER1 plays different roles depending on cell context, but is thought to be a functional tumour suppressor gene. Accordingly, germline mutation in one DICER1 allele is insufficient for oncogenesis, and a second hit on the other allele is required, as a result of postnatal somatic mutation. Loss of DICER1 is linked to multiple tumours, with prominent endocrine representation. Multinodular goitre is frequent, with increased risk of differentiated thyroid cancer. Rare, developmental pituitary tumours are reported, including pituitary blastoma, but not reports of functional pituitary adenomas. As DICER1 mutations are rare, case reports are the only means to identify new manifestations and to inform appropriate screening protocols.
DICER1 mutations lead to endocrine tumours.
DICER1 is required for small non-coding RNA expression.
DICER1 carriage and microprolactinoma are both rare, but here are reported in the same individual, suggesting association.
Endocrine follow-up of patients carrying DICER1 mutations should consider pituitary disease.
Kallmann syndrome (KS) is a form of hypogonadotropic hypogonadism in combination with a defect in sense of smell, due to abnormal migration of gonadotropin-releasing hormone-producing neurons. We report a case of a 17-year-old Tunisian male who presented with eunuchoid body proportions, absence of facial, axillary and pubic hair, micropenis and surgically corrected cryptorchidism. Associated findings included anosmia. Karyotype was 46XY and hormonal measurement hypogonadotropic hypogonadism. MRI of the brain showed bilateral agenesis of the olfactory bulbs and 3.5 mm pituitary microadenoma. Hormonal assays showed no evidence of pituitary hypersecretion.
The main clinical characteristics of KS include hypogonadotropic hypogonadism and anosmia or hyposmia.
MRI, as a non-irradiating technique, should be the first radiological step for investigating the pituitary gland as well as abnormalities of the ethmoid, olfactory bulbs and tracts in KS.
KS may include anterior pituitary hypoplasia or an empty sella syndrome. The originality of our case is that a microadenoma also may be encountered in KS. Hormonal assessment indicated the microadenoma was non-functioning. This emphasizes the importance of visualizing the pituitary region in KS patients to assess for hypoplastic pituitary malformations or adenomas.
Graves’ disease, the most common form of hyperthyroidism in iodine-replete countries, is associated with the presence of immunoglobulins G (IgGs) that are responsible for thyroid growth and hyperfunction. In this article, we report the unusual case of a patient with acromegaly and a severe form of Graves’ disease. Here, we address the issue concerning the role of growth hormone (GH) and insulin-like growth factor 1 (IGF1) in influencing thyroid function. Severity of Graves’ disease is exacerbated by coexistent acromegaly and both activity indexes and symptoms and signs of Graves’ disease improve after the surgical remission of acromegaly. We also discuss by which signaling pathways GH and IGF1 may play an integrating role in regulating the function of the immune system in Graves’ disease and synergize the stimulatory activity of Graves’ IgGs.
Clinical observations have demonstrated an increased prevalence of euthyroid and hyperthyroid goiters in patients with acromegaly.
The coexistence of acromegaly and Graves’ disease is a very unusual event, the prevalence being <1%.
Previous in vitro studies have showed that IGF1 synergizes the TSH-induced thyroid cell growth-activating pathways independent of TSH/cAMP/PKA cascade.
We report the first case of a severe form of Graves’ disease associated with acromegaly and show that surgical remission of acromegaly leads to a better control of symptoms of Graves’ disease.
Co-secretion of growth hormone (GH) and prolactin (PRL) from a single pituitary adenoma is common. In fact, up to 25% of patients with acromegaly may have PRL co-secretion. The prevalence of acromegaly among patients with a newly diagnosed prolactinoma is unknown. Given the possibility of mixed GH and PRL co-secretion, the current recommendation is to obtain an insulin-like growth factor-1 (IGF-1) in patients with prolactinoma at the initial diagnosis. Long-term follow-up of IGF-1 is not routinely done. Here, we report two cases of well-controlled prolactinoma on dopamine agonists with the development of acromegaly 10–20 years after the initial diagnoses. In both patients, a mixed PRL/GH-cosecreting adenoma was confirmed on the pathology examination after transsphenoidal surgery (TSS). Therefore, periodic routine measurements of IGF-1 should be considered regardless of the duration and biochemical control of prolactinoma.
Acromegaly can develop in patients with well-controlled prolactinoma on dopamine agonists.
The interval between prolactinoma and acromegaly diagnoses can be several decades.
Periodic screening of patients with prolactinoma for growth hormone excess should be considered and can lead to an early diagnosis of acromegaly before the development of complications.
In this report, we describe a female patient with both prolactinoma and psychotic disorder who was successfully treated with aripiprazole, a partial dopamine 2 receptor agonist. During the follow-up of more than 10 years, her psychotic symptoms improved considerably, prolactin levels normalised and the size of the prolactinoma decreased. This observation may be of clinical relevance in similar patients who often are difficult to treat with the regular dopaminergic drugs.
Prolactinoma coinciding with psychosis can represent a therapeutic challenge.
In contrast to many other antipsychotic drugs, aripiprazole is associated with a decrease in prolactin levels.
Aripiprazole can be a valuable pharmaceutical tool to treat both prolactinoma and psychosis.
Jenny E GuntonDepartment of Diabetes and Endocrinology, Westmead Hospital, Sydney, 2145, Australia Faculty of Medicine, Westmead Hospital, University of Sydney, Sydney, 2145, Australia St Vincent's Clinical School, University of New South Wales, Sydney, 2010, Australia Diabetes and Transcription Factors Group, Garvan Institute of Medical Research (GIMR), Sydney, 2010, Australia Department of Diabetes, Obesity and Endocrinology, The Westmead Institute for Medical Research, The University of Sydney, Sydney, 2045, Australia
Ketoconazole was a first-line agent for suppressing steroidogenesis in Cushing's disease. It now has limited availability. Fluconazole, another azole antifungal, is an alternative, although its in vivo efficacy is unclear. A 61-year-old female presented with weight gain, abdominal striae and worsening depression. HbA1c increased to 76 mmol/mol despite increasing insulin. Investigations confirmed cortisol excess; afternoon serum cortisol was 552 nmol/l with an inappropriate ACTH of 9.3 pmol/l. In total, 24-h urinary free cortisol (UFC):creatinine ratio was 150 nmol/mmol with failure to suppress after 48 h of low-dose dexamethasone. Pituitary MRI revealed a 4-mm microadenoma. Inferior petrosal sinus sampling confirmed Cushing's disease. Transsphenoidal resection was performed and symptoms improved. However, disease recurred 6 months later with elevated 24-h UFC >2200 nmol/day. Metyrapone was commenced at 750 mg tds. Ketoconazole was later added at 400 mg daily, with dose reduction in metyrapone. When ketoconazole became unavailable, fluconazole 200 mg daily was substituted. Urine cortisol:creatinine ratio rose, and the dose was increased to 400 mg daily with normalisation of urine hormone levels. Serum cortisol and urine cortisol:creatinine ratios remain normal on this regimen at 6 months. In conclusion, to our knowledge, this is the first case demonstrating prolonged in vivo efficacy of fluconazole in combination with low-dose metyrapone for the treatment of Cushing's disease. Fluconazole has a more favourable toxicity profile, and we suggest that it is a potential alternative for medical management of Cushing's disease.
Surgery remains first line for the management of Cushing's disease with pharmacotherapy used where surgery is unsuccessful or there is persistence of cortisol excess.
Ketoconazole has previously been used to treat cortisol excess through inhibition of CYP450 enzymes 11-β-hydroxylase and 17-α-hydroxylase, though its availability is limited in many countries.
Fluconazole shares similar properties to ketoconazole, although it has less associated toxicity.
Fluconazole represents a suitable alternative for the medical management of Cushing's disease and proved an effective addition to metyrapone in the management of this case.