Diagnosis and Treatment > Signs and Symptoms > Cold intolerance
You are looking at 1 - 6 of 6 items
Search for other papers by Ploutarchos Tzoulis in
Google Scholar
PubMed
Search for other papers by Richard W Corbett in
Google Scholar
PubMed
Search for other papers by Swarupini Ponnampalam in
Google Scholar
PubMed
Search for other papers by Elly Baker in
Google Scholar
PubMed
Search for other papers by Daniel Heaton in
Google Scholar
PubMed
Search for other papers by Triada Doulgeraki in
Google Scholar
PubMed
Search for other papers by Justin Stebbing in
Google Scholar
PubMed
Summary
Five days following the 3rd cycle of nivolumab, a monoclonal antibody, which acts as immune checkpoint inhibitor against the programmed cell death protein-1, for metastatic lung adenocarcinoma, a 56-year-old woman presented at the hospital critically ill. On admission, she had severe diabetic ketoacidosis (DKA), as evidenced by venous glucose of 47 mmol/L, blood ketones of 7.5 mmol/L, pH of 6.95 and bicarbonate of 6.6 mmol/L. She has had no personal or family history of diabetes mellitus (DM), while random venous glucose, measured 1 week prior to hospitalisation, was 6.1 mmol/L. On admission, her HbA1c was 8.2% and anti-GAD antibodies were 12 kIU/L (0–5 kU/L), while islet cell antibodies and serum C-peptide were undetectable. Nivolumab was recommenced without the development of other immune-mediated phenomena until 6 months later, when she developed hypothyroidism with TSH 18 U/L and low free T4. She remains insulin dependent and has required levothyroxine replacement, while she has maintained good radiological and clinical response to immunotherapy. This case is notable for the rapidity of onset and profound nature of DKA at presentation, which occurred two months following commencement of immunotherapy. Despite the association of nivolumab with immune-mediated endocrinopathies, only a very small number of patients developing type 1 DM has been reported to date. Patients should be closely monitored for hyperglycaemia and thyroid dysfunction prior to and periodically during immunotherapy.
Learning points:
-
Nivolumab can induce fulminant type 1 diabetes, resulting in DKA.
-
Nivolumab is frequently associated with thyroid dysfunction, mostly hypothyroidism.
-
Nivolumab-treated patients should be monitored regularly for hyperglycaemia and thyroid dysfunction.
-
Clinicians should be aware and warn patients of potential signs and symptoms of severe hyperglycaemia.
Search for other papers by Nicole Maison in
Google Scholar
PubMed
Search for other papers by Esther Korpershoek in
Google Scholar
PubMed
Search for other papers by Graeme Eisenhofer in
Google Scholar
PubMed
Search for other papers by Mercedes Robledo in
Google Scholar
PubMed
Department of Pathology, Reinier de Graaf Hospital, Delft, The Netherlands
Search for other papers by Ronald de Krijger in
Google Scholar
PubMed
Search for other papers by Felix Beuschlein in
Google Scholar
PubMed
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.
Search for other papers by W C Candy Sze in
Google Scholar
PubMed
Search for other papers by Joe McQuillan in
Google Scholar
PubMed
Search for other papers by P Nicholas Plowman in
Google Scholar
PubMed
Search for other papers by Niall MacDougall in
Google Scholar
PubMed
Search for other papers by Philip Blackburn in
Google Scholar
PubMed
Search for other papers by H Ian Sabin in
Google Scholar
PubMed
Search for other papers by Nadeem Ali in
Google Scholar
PubMed
Search for other papers by William M Drake in
Google Scholar
PubMed
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.
Hormones and Cancer Group, Garvan Institute of Medical Research, 384 Victoria Street, Sydney, New South Wales, 2010, Australia
Search for other papers by Sunita M C De Sousa in
Google Scholar
PubMed
Search for other papers by Peter Earls in
Google Scholar
PubMed
Hormones and Cancer Group, Garvan Institute of Medical Research, 384 Victoria Street, Sydney, New South Wales, 2010, Australia
Search for other papers by Ann I McCormack in
Google Scholar
PubMed
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.
Search for other papers by Mohammed Al-Sofiani in
Google Scholar
PubMed
Search for other papers by Dhimitri Nikolla in
Google Scholar
PubMed
Search for other papers by V V S Ramesh Metta in
Google Scholar
PubMed
Summary
We report the case of a 42-year-old female with a history of hypothyroidism and asthma presenting with progressive dyspnea and orthopnea after 2 days of an upper respiratory tract infection (URTI). Based on the clinical and radiological findings, the patient was admitted as a case of cardiogenic pulmonary edema secondary to possible viral myocarditis. However, a normal brain natriuretic peptide (BNP) level with a normal ejection fraction (EF) on echocardiogram changed our working diagnosis from cardiogenic to non-cardiogenic pulmonary edema. Further questioning revealed a history of nocturnal snoring, frequent awakening, and daytime fatigue, suggesting a possible sleep apnea syndrome (SAS). In conclusion, we believe that SAS was the missing link between our patient's hypothyroidism and non-cardiogenic pulmonary edema.
Learning points
-
Always keep an open mind and look for a pathology that would explain the whole clinical scenario.
-
The involvement of the respiratory system in hypothyroidism can range from SAS, pulmonary hypertension, hypoventilation, and severe respiratory failure.
-
Hypothyroidism and SAS should be considered in the differential diagnosis of non-cardiogenic pulmonary edema.
-
Patients should be instructed to take levothyroxine on an empty stomach 30–60 min before food to avoid erratic absorption of the hormone.
Search for other papers by Gerald J M Tevaarwerk in
Google Scholar
PubMed
Summary
Low triiodothyronine (T3) concentrations in the presence of normal thyroxine (T4) and TSH levels, referred to as the low T3 syndrome (LT3S), are common. LT3S may be caused by starvation, various non-thyroidal illnesses (NTIs) and some medications. Reverse T3 (rT3) concentrations are elevated in the more severely ill, and they characteristically fail to respond to exogenous levothyroxine (l-T4) therapy. The biochemical abnormalities have been explained on the basis of altered peripheral deiodinase activities. Herein, we report on two patients with hypothyroid symptoms who on testing were found to have LT3S. They were atypical clinically in not having LT3S due to any of the usual causes, had no increased rT3 concentrations, and had a normal negative TSH feedback response to l-T4. One (patient 1) had previously been diagnosed with Hashimoto's autoimmune primary hypothyroidism and was on l-T4 therapy. Both had T4 concentrations in the reference range. TSH levels were elevated in patient 1 and in the reference range in patient 2. Starting or increasing l-T4 doses resulted in no clinical improvement and no increase in T3 levels in spite of a marked increase in T4 levels. It is suggested that in the absence of the usual causes, lack of elevated rT3 levels, response to treatment and intact negative TSH feedback these two patients differ from the usual secondary causes of decreases in deiodinase activity. It is speculated that they may represent primary alterations in deiodinase enzymes possibly due to genetic variations in the deiodinase-encoding genes.
Learning points
-
LT3S is commonly found secondary to starvation, NTIs and use of some medications.
-
Low T3 levels are the result of alterations in the activity of deiodinase enzymes.
-
LT3S without the usual causes may represent a primary disturbance in deiodinase activity.
