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Open access

A serious and unusual presentation of congenital isolated ACTH deficiency due to TBX19 mutation, beyond the neonatal period

Inês Henriques Vieira, Nádia Mourinho Bala, Fabiana Ramos, Isabel Dinis, Rita Cardoso, Joana Serra Caetano, Dírcea Rodrigues, Isabel Paiva, and Alice Mirante

Summary

Congenital isolated adrenocorticotrophic hormone (ACTH) deficiency due to T-box transcription factor-19 (TBX19 mutation) (MIM 201400; ORPHA 199296) usually presents in the neonatal period with severe hypoglycemia, seizures, and sometimes prolonged cholestatic jaundice. We report a case with an unusual presentation that delayed the diagnosis. A 9-month-old female patient with no relevant personal history was admitted to the emergency department due to a hypoglycemic seizure in the context of acute gastroenteritis. There was rapid recovery after glucose administration. At age 4, she presented with tonic-clonic seizures, fever, and gastrointestinal symptoms and came to need support in an intensive care unit. Low serum cortisol was documented and hydrocortisone was initiated. After normalization of inflammatory parameters, the patient was discharged with hydrocortisone. The genetic investigation was requested and compound heterozygous mutations in TBX19 were detected. This is a rare case of presentation of TBX19 mutation outside the neonatal period and in the setting of acute disease, which presented a diagnostic challenge.

Learning points

  • Congenital isolated adrenocorticotrophic hormone deficiency due to TBX19 mutation usually presents with neonatal hypoglycemia and prolonged cholestatic jaundice.

  • An uneventful neonatal period, however, does not exclude the diagnosis as the disease may be asymptomatic at this stage.

  • In the context of idiopathic hypoglycemia, even in the context of acute disease, hypocortisolism must always be excluded.

  • Genetic evaluation should be performed in cases of congenital central hypocortisolism to allow proper counselling.

Open access

Novel TSHB variant (c.217A>C) causing severe central hypothyroidism and pituitary hyperplasia

Adam I Kaplan, Catherine Luxford, and Roderick J Clifton-Bligh

Summary

Biallelic pathological variants in the thyroid stimulating hormone (TSH) subunit β gene (TSHB) result in isolated TSH deficiency and secondary hypothyroidism, a rare form of central congenital hypothyroidism (CCH), with an estimated incidence of 1 in 65 000 births. It is characterised by low levels of free thyroxine and inappropriately low serum TSH and may therefore be missed on routine neonatal screening for hypothyroidism, which relies on elevated TSH. We describe a patient with CCH who developed recurrence of pituitary hyperplasia and symptomatic hypothyroidism due to poor compliance with thyroxine replacement. She was diagnosed with CCH as a neonate and had previously required trans-sphenoidal hypophysectomy surgery for pituitary hyperplasia associated with threatened chiasmal compression at 17 years of age due to variable adherence to thyroxine replacement. Genetic testing of TSHB identified compound heterozygosity with novel variant c.217A>C, p.(Thr73Pro), and a previously reported variant c.373delT, p.(Cys125Valfs*10). Continued variable adherence to treatment as an adult resulted in recurrence of significant pituitary hyperplasia, which subsequently resolved with improved compliance without the need for additional medications or repeat surgery. This case describes a novel TSHB variant associated with CCH and demonstrates the importance of consistent compliance with thyroxine replacement to treat hypothyroidism and prevent pituitary hyperplasia in central hypothyroidism.

Learning points

  • Pathogenic variants in the TSH subunit β gene (TSHB) are rare causes of central congenital hypothyroidism (CCH).

  • c.217A>C, p.(Thr73Pro), is a novel TSHB variant, presented in association with CCH in this case report.

  • Thyroxine replacement is critical to prevent clinical hypothyroidism and pituitary hyperplasia.

  • Pituitary hyperplasia can recur post-surgery if adherence to thyroxine replacement is not maintained.

  • Pituitary hyperplasia can dramatically reverse if compliance with thyroxine replacement is improved to maintain free thyroxine (FT4) levels in the middle-to-upper normal range, without the need for additional medications or surgeries.

Open access

Adult-onset Langerhans cell histiocytosis changing CNS lesion from pituitary to suprasellar extension

Yuji Kadowaki, Mitsuru Nishiyama, Makoto Nakamura, Hiroyuki Morisaka, Shimpei Fujimoto, Yoshio Terada, and Kensuke Kojima

Summary

Langerhans cell histiocytosis (LCH) is a rare disease characterized by the proliferation of abnormal Langerhans cells in various tissues and organs, including bone, skin, the lungs, and the pituitary gland. Hypothalamic–pituitary lesions in LCH often cause central diabetes insipidus (CDI), but the natural course of LCH in the CNS remains to be elucidated. In this study, we report an interesting case of altered LCH lesions in the CNS from the pituitary to the hypothalamus in a 45-year-old woman. She developed symptoms of polyuria and was diagnosed with CDI with lymphocytic hypophysitis due to an enlarged pituitary gland with stalk thickening shown on MRI. Short-term glucocorticoid therapy cured pituitary enlargement, but serum prolactin levels gradually increased. Six years later, the immunohistological findings of a skin biopsy revealed positive for leukocyte common antigen, S-100, and CD1a expression, indicating a diagnosis of LCH. MRI revealed a new lesion in the hypothalamus without pituitary involvement, likely due to LCH. Chemotherapy improved LCH lesions both in the skin and hypothalamus, but therapy was stopped on the patient’s request. Although adult-onset LCH is rare, it should be considered as a differential diagnosis in cases of CDI as the primary disease. The clinical course in the present case indicated that LCH lesion was altered from pituitary to suprasellar extension; where such changes were observed, the possibility of LCH should be considered.

Learning points

  • Diagnosing the primary disease of CDI is challenging; therefore, careful observation is necessary in pathologically unknown cases.

  • Enhanced MRI should be performed in cases with suspected hypothalamic lesions, such as elevated serum prolactin.

  • Although adult-onset LCH is rare, it should be considered a differential diagnosis in cases of CDI as the primary disease.

  • The direction of changing CNS lesion from pituitary to suprasellar extension might be a unique MRI finding in LCH.

Open access

An altered state of consciousness while using anticoagulants and the incidental discovery of a pituitary lesion: considering pituitary apoplexy

N Viola, C Urbani, M Cosottini, A Abruzzese, L Manetti, G Cosentino, G Marconcini, C Marcocci, F Bogazzi, and I Lupi

Summary

Pituitary apoplexy (PA) is a medical emergency with complex diagnosis and management. In this study, we describe a case of PA in a 63-year-old male treated with oral anticoagulant therapy for atrial fibrillation. In the patient, PA manifested itself with asthenia and severe headache not responsive to common analgesics. Despite the finding of a pituitary mass through CT, and in anticipation of the endocrinological evaluation and pituitary MRI, the patient’s clinical condition worsened with an escalation of headache and asthenia associated with deterioration of the visual field and impairment of consciousness level. The emergency assessments revealed an adrenal failure, whereas MRI showed a haemorrhagic pituitary macroadenoma with compression of the optic chiasm. Intravenous fluids repletion and high-dose hydrocortisone were started with a rapid improvement of the patient’s health and visual field abnormalities. Hydrocortisone was gradually reduced to a replacement dose. During the follow-up, panhypopituitarism was documented, and replacement therapies with l-thyroxine and testosterone were introduced. Three months later, a pituitary MRI showed a 50% reduction in the pituitary adenoma volume.

Learning points

  • Pituitary apoplexy (PA) is a medical emergency that can result in haemodynamic instability and abnormalities in the level of consciousness.

  • The management of PA requires a multidisciplinary team that includes endocrinologists, ophthalmologists, neuro-radiologists, and neuro-surgeons.

  • Pituitary MRI with gadolinium is the diagnostic gold standard for PA.

  • PA therapy aims to improve general conditions and treat compression symptoms, especially visual field abnormalities.

  • Adrenocorticotrophic hormone deficiency is a common and severe complication of PA. Thus, all patients with PA must be promptly treated with injective synthetic glucocorticoids (e.g. hydrocortisone 100 mg) and i.v. saline.

  • PA must be taken into consideration in case of sudden headache in patients with a pituitary macroadenoma, especially if other risk factors are recognized.

Open access

Ischemic stroke: a rare complication of a large multinodular goiter

Yudi Camacho, Yusra Jamal, Andy Wang, Patrick Chiarolanzio, and Gayotri Goswami

Summary

Mass effect from a goiter is a serious complication with potentially life-threatening consequences. In rare instances, a goiter can compress nearby vessels, compromising cerebral blood flow, which can lead to an ischemic stroke. Ischemic strokes generally occur due to atherogenic or embolic phenomenon, albeit a rare etiology can be due to a mechanical obstruction of great vessels of the neck that provide blood supply to the brain. An unusual example of a similar obstruction is the mass effect of an expansive goiter on the carotid artery (CA) in the neck. We present a rare case of a 90-year-old female who had a historically untreated goiter for 13 years. She presented with symptoms of acute stroke, including right-sided weakness and dysarthria. CT angiogram of the neck revealed a massively enlarged thyroid gland causing compression and intermittent obstruction of the blood flow in the left common CA. Subsequently, the patient underwent a total thyroidectomy. Postoperatively, she had a remarkable recovery of her symptoms of right-sided weakness and dysarthria. Acknowledging stroke as a grave mechanical complication of a large multinodular goiter is crucial for timely and appropriate management to avoid serious consequences.

Learning points

  • The natural history of euthyroid multinodular goiters include abnormal enlargement of the thyroid gland, which results in local compression of structures in the neck causing neurovascular injury.

  • Timely diagnosis and surgical management of an enlarging goiter compressing the CA can reduce morbidity from an ischemic stroke.

  • Ischemic stroke is a rare and dangerous complication of a giant multinodular goiter.

Open access

Graves’ disease in an adolescent presenting with increased intracranial pressure and bilateral papilledema

Jay Nguyen and Dennis Joseph

Summary

Increased intracranial pressure (ICP) can present with symptoms of headache, vomiting, visual changes, and tinnitus. Papilledema may be seen on physical exam. Thyroid disease has been a rare secondary cause of increased ICP. We present a 16-year-old female who had a worsening headache for 6 months. She was found to have signs, symptoms, physical exam findings, and diagnostic studies consistent with both increased ICP and previously undiagnosed Graves’ disease. The patient was treated with a 19-month course of methimazole 40 mg daily. Her headache and papilledema resolved shortly after medication initiation. The timeline of symptoms and resolution of her increased ICP symptoms with treatment of Graves’ disease suggests that hyperthyroidism was the underlying cause of her increased ICP. Clinicians should consider Graves’ disease as the etiology in pediatric patients presenting with signs and symptoms of increased ICP with papilledema.

Learning points

  • Symptoms of increased intracranial pressure (ICP) include headache, vomiting, transient visual changes, and tinnitus.

  • Secondary causes of increased ICP should be considered in males, young children, older patients, and those not overweight.

  • Clinicians should consider Graves’ disease as the etiology in pediatric patients presenting with signs and symptoms of increased ICP with papilledema. They should assess for orbitopathy and thyromegaly and inquire about symptoms that would be indicative of hyperthyroidism.

Open access

A rare case of 46,XX gonadal dysgenesis, Mayer–Rokitansky–Kuster–Hauser syndrome, pituitary and thyroid hypoplasia

Rediet Ambachew, Amare Gulilat, Tewodros Aberra, Zewdu Terefework, Wubalem Bedilu, Getahun Tarekegn, and Ahmed Reja

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.

Open access

Dual attack: targeting the rare co-occurrence of myasthenia gravis and Graves’ disease with radioactive iodine therapy

Anna Elvira S Arcellana, Karen Joy B Adiao, and Myrna Buenaluz-Sedurante

Summary

Occasionally, autoimmune disorders can come in twos. This double trouble creates unique challenges. Myasthenia gravis co-existing with autoimmune thyroid disease occurs in only about 0.14–0.2% of cases. The patient is a 27-year-old man with a 2-month history of bilateral ptosis, diplopia, with episodes of easy fatigability, palpitations, and heat intolerance. On physical exam, the patient had an enlarged thyroid gland. Myasthenia gravis was established based on the presence of ptosis with weakness of the intraocular muscles, abnormal fatigability, and a repetitive nerve stimulation study indicated neuromuscular junction disease. Episodes of fluctuating right shoulder weakness were also noted. He was also found to have elevated FT3, FT4, and a suppressed TSH. Thyroid ultrasound revealed thyromegaly with diffused parenchymal disease. Thyroid scintigraphy showed increased uptake function at 72.4% uptake at 24 h. TRAb was positive at 4.1 U/L. Patient was started on pyridostigmine which led to a significant reduction in the frequency of ocular muscle weakness. Methimazole was also initiated. Radioactive iodine at 14.9 mci was instituted for the definitive management of hyperthyroidism. After RAI, there was abatement of the hyperthyroid symptoms, as well as improvement in the status of the myasthenia gravis, with ptosis, diplopia, and right arm weakness hardly occurring thereafter despite the reduction of the pyridostigmine dose based on a symptom diary and medication intake record. Two distinct autoimmune conditions displayed a markedly improved clinical course with the institution of radioactive iodine therapy for Graves’ disease.

Learning points

  • The presence of ptosis, diplopia, and fluctuating muscle weakness are atypical in Graves’ disease and should prompt an investigation on the existence of concurrent myasthenia gravis. A prompt diagnosis of both conditions will enable the institution of appropriate management that would target both rare and challenging autoimmune diseases.

  • Selecting the therapeutic options with minimal risk of morbidity and mortality, which could lead to maximal benefit especially in a resource-limited setting is paramount.

  • Targeted non-surgical management can lead to the remission of two autoimmune diseases which can result in patient satisfaction and improved quality of life.

Open access

Glucokinase activating mutation causing hypoglycaemia diagnosed late in adult who fasts for Ramadhan

Wann Jia Loh, Lily Mae Dacay, Clara Si Hua Tan, Su Fen Ang, Fabian Yap, Su Chi Lim, and Joan Khoo

Summary

Activating mutation of glucokinase gene (GCK) causes resetting of insulin inhibition at a lower glucose threshold causing hyperinsulinaemic hypoglycaemia (GCK-HH). This is the first reported case who tolerated years of regular fasting during Ramadhan, presenting only with seizure and syncope now. We describe a case with GCK gene variant p.T65I diagnosed in a 51-year-old woman with hypoglycaemia unawareness even at glucose level of 1.6 mmol/L. Insulin and C-peptide levels during hypoglycaemia were suggestive of hyperinsulinism, but at a day after intravenous glucagon, hypoglycaemia occurred with low insulin and C-peptide levels, pointing against insulinoma as the underlying aetiology. Imaging studies of the pancreas and calcium arterial stimulation venous sampling were unremarkable. A review of old medical records revealed asymptomatic hypoglycaemia years ago. Genetic testing confirmed activating mutation of GCK. Hypoglycaemia was successfully controlled with a somatostatin analogue. This case highlights the importance of consideration of genetic causes of hypoglycaemia in adulthood, especially when imaging is uninformative.

Learning points

  • Consider genetic causes of endogenous hyperinsulinism hypoglycaemia in adulthood, especially when imaging is uninformative.

  • Late presentation of activating mutation of GCK can occur because of hypoglycaemia unawareness.

  • Long-acting somatostatin analogue may be useful for the treatment of activating mutation of GCK causing hypoglycaemia.

  • Depending on the glucose level when the blood was taken, and the threshold of glucose-stimulated insulin release (GSIR), the serum insulin and C-peptide levels may be raised (hyperinsulinaemic) or low (hypoinsulinaemic) in patients with activating mutation of GCK.

  • Glucagon may be useful to hasten the process of unmasking the low insulin level during hypoglycaemia below the GSIR level of which insulin released is suppressed.

Open access

Myxedema coma complicated by bilateral hygromas

Ann-Elin Meling Stokland, Anne Lise Dahle, Vidar Laurits Kloster, Torbjørn Nedrebø, and Bjørn Gunnar Nedrebø

Summary

Myxedema coma is an important differential diagnosis in critically ill patients. Early diagnosis and treatment are paramount but challenging due to a lack of diagnostic criteria. We report a case about a patient who suffered from untreated hypothyroidism for several years. Before the correct diagnosis was made, he was admitted three times due to severe constipation. Eventually, he developed myxedema coma in connection with a urinary tract infection. The course was complicated by recurrent seizures, and neuroimaging showed bilateral hygromas. Hormone replacement therapy resulted in complete recovery and regression of hygromas. To the best of our knowledge, this is the first time hygroma is reported in association with myxedema coma.

Learning points

  • Myxedema coma is a difficult diagnosis to make due to a lack of diagnostic criteria.

  • Cardinal features include hypothermia, bradycardia, gastrointestinal symptoms, pericardial/pleural effusions and affection of CNS. Anemia and hyponatremia are common.

  • In case of suspected myxedema coma, neuroimaging should be a part of the evaluation in most cases.

  • There is a possible association between longstanding/severe hypothyroidism and hygroma.