Diagnosis and Treatment > Medication
Search for other papers by Wei Yang in
Google Scholar
PubMed
Search for other papers by David Pham in
Google Scholar
PubMed
Search for other papers by Aren T Vierra in
Google Scholar
PubMed
Search for other papers by Sarah Azam in
Google Scholar
PubMed
Search for other papers by Dorina Gui in
Google Scholar
PubMed
Search for other papers by John C Yoon in
Google Scholar
PubMed
Summary
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.
Learning points:
-
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.
Department of Endocrinology, Royal Hospital for Sick Children, Edinburgh, UK
Search for other papers by Sarah Kiff in
Google Scholar
PubMed
Search for other papers by Carolyn Babb in
Google Scholar
PubMed
Genetics and Genomic Medicine Programme, Great Institute of Child Health, University College London, London, UK
Search for other papers by Maria Guemes in
Google Scholar
PubMed
Search for other papers by Antonia Dastamani in
Google Scholar
PubMed
Search for other papers by Clare Gilbert in
Google Scholar
PubMed
Search for other papers by Sarah E Flanagan in
Google Scholar
PubMed
Search for other papers by Sian Ellard in
Google Scholar
PubMed
Search for other papers by John Barton in
Google Scholar
PubMed
Genetics and Genomic Medicine Programme, Great Institute of Child Health, University College London, London, UK
Search for other papers by M Dattani in
Google Scholar
PubMed
Genetics and Genomic Medicine Programme, Great Institute of Child Health, University College London, London, UK
Search for other papers by Pratik Shah in
Google Scholar
PubMed
Summary
We report a case of partial diazoxide responsiveness in a child with severe congenital hyperinsulinaemic hypoglycaemia (CHI) due to a homozygous ABCC8 mutation. A term baby, with birth weight 3.8 kg, born to consanguineous parents presented on day 1 of life with hypoglycaemia. Hypoglycaemia screen confirmed CHI. Diazoxide was commenced on day 7 due to ongoing elevated glucose requirements (15 mg/kg/min), but despite escalation to a maximum dose (15 mg/kg/day), intravenous (i.v.) glucose requirement remained high (13 mg/kg/min). Genetic testing demonstrated a homozygous ABCC8 splicing mutation (c.2041-1G>C), consistent with a diffuse form of CHI. Diazoxide treatment was therefore stopped and subcutaneous (s.c.) octreotide infusion commenced. Despite this, s.c. glucagon and i.v. glucose were required to prevent hypoglycaemia. A trial of sirolimus and near-total pancreatectomy were considered, however due to the significant morbidity potentially associated with these, a further trial of diazoxide was commenced at 1.5 months of age. At a dose of 10 mg/kg/day of diazoxide and 40 µg/kg/day of octreotide, both i.v. glucose and s.c. glucagon were stopped as normoglycaemia was achieved. CHI due to homozygous ABCC8 mutation poses management difficulties if the somatostatin analogue octreotide is insufficient to prevent hypoglycaemia. Diazoxide unresponsiveness is often thought to be a hallmark of recessively inherited ABCC8 mutations. This patient was initially thought to be non-responsive, but this case highlights that a further trial of diazoxide is warranted, where other available treatments are associated with significant risk of morbidity.
Learning points:
-
Homozygous ABCC8 mutations are commonly thought to cause diazoxide non-responsive hyperinsulinaemic hypoglycaemia.
-
This case highlights that partial diazoxide responsiveness in homozygous ABCC8 mutations may be present.
-
Trial of diazoxide treatment in combination with octreotide is warranted prior to considering alternative treatments, such as sirolimus or near-total pancreatectomy, which are associated with more significant side effects.
Search for other papers by Katia Regina Marchetti in
Google Scholar
PubMed
Search for other papers by Maria Adelaide Albergaria Pereira in
Google Scholar
PubMed
Search for other papers by Arnaldo Lichtenstein in
Google Scholar
PubMed
Search for other papers by Edison Ferreira Paiva in
Google Scholar
PubMed
Summary
Adrenacarcinomas are rare, and hypoglycemic syndrome resulting from the secretion of insulin-like growth factor II (IGF-II) by these tumors have been described infrequently. This study describes the case of a young woman with severe persistent hypoglycemia and a large adrenal tumor and discusses the physiopathological mechanisms involved in hypoglycemia. The case is described as a 21-year-old woman who presented with 8 months of general symptoms and, in the preceding 3 months, with episodes of mental confusion and visual blurring secondary to hypoglycemia. A functional assessment of the adrenal cortex revealed ACTH-independent hypercortisolism and hyperandrogenism. Hypoglycemia, hypoinsulinemia, low C-peptide and no ketones were also detected. An evaluation of the GH–IGF axis revealed GH blockade (0.03; reference: up to 4.4 ng/mL), greatly reduced IGF-I levels (9.0 ng/mL; reference: 180–780 ng/mL), slightly reduced IGF-II levels (197 ng/mL; reference: 267–616 ng/mL) and an elevated IGF-II/IGF-I ratio (21.9; reference: ~3). CT scan revealed a large expansive mass in the right adrenal gland and pulmonary and liver metastases. During hospitalization, the patient experienced frequent difficult-to-control hypoglycemia and hypokalemia episodes. Octreotide was ineffective in controlling hypoglycemia. Due to unresectability, chemotherapy was tried, but after 3 months, the patient’s condition worsened and progressed to death. In conclusion, our patient presented with a functional adrenal cortical carcinoma, with hyperandrogenism associated with hypoinsulinemic hypoglycemia and blockage of the GH–IGF-I axis. Patient’s data suggested a diagnosis of hypoglycemia induced by an IGF-II or a large IGF-II-producing tumor (low levels of GH, greatly decreased IGF-I, slightly decreased IGF-II and an elevated IGF-II/IGF-I ratio).
Learning points:
-
Hypoglycemyndrome resulting from the secretion of insulin-like growth factor II (IGF-II) by adrenal tumors is a rare condition.
-
Hypoinsulinemic hypoglycemia associated with hyperandrogenism and blockage of the GH–IGF-I axis suggests hypoglycemia induced by an IGF-II or a large IGF-II-producing tumor.
-
Hypoglycemia in cases of NICTH should be treated with glucocorticoids, glucagon, somatostatin analogs and hGH.
Search for other papers by F Serra in
Google Scholar
PubMed
Search for other papers by S Duarte in
Google Scholar
PubMed
Search for other papers by S Abreu in
Google Scholar
PubMed
Search for other papers by C Marques in
Google Scholar
PubMed
Search for other papers by J Cassis in
Google Scholar
PubMed
Search for other papers by M Saraiva in
Google Scholar
PubMed
Summary
Ectopic secretion of ACTH is an infrequent cause of Cushing's syndrome. We report a case of ectopic ACTH syndrome caused by a nasal paraganglioma, a 68-year-old female with clinical features of Cushing's syndrome, serious hypokalaemia and a right paranasal sinus' lesion. Cranial magnetic resonance image showed a 46-mm mass on the right paranasal sinuses. Endocrinological investigation confirmed the diagnosis of ectopic ACTH production. Resection of the tumour normalised ACTH and cortisol secretion. The tumour was found to be a paraganglioma through microscopic analysis. On follow-up 3 months later, the patient showed nearly complete clinical recovery. Ectopic ACTH syndrome due to nasal paraganglioma is extremely uncommon, as only two other cases have been discussed in the literature.
Learning points
-
Ectopic Cushing's syndrome accounts for 10% of Cushing's syndrome etiologies.
-
Most paraganglioma of the head and neck are not hormonally active.
-
Nasal paraganglioma, especially ACTH producing, is a very rare tumour.
