Maturation in Serum Thyroid Function Parameters Over Childhood and Puberty: Results of a Longitudinal Study.

Context: Serum thyroid hormone levels differ between children and adults, but have not been studied longitudinally through childhood. Objective: To assess changes in thyroid-stimulating hormone (TSH) and thyroid hormone levels over childhood and their interrelationships. Design: Cohort study. Setting: The Avon Longitudinal Study of Parents and Children, a population-based birth cohort. Participants: A total of 4442 children who had thyroid function measured at age 7, and 1263 children who had thyroid function measured at age 15. Eight hundred eighty-four children had measurements at both ages. Main Outcome Measures: Reference ranges for TSH, free tri-iodothyronine (FT3), free thyroxine (FT4), their longitudinal stability, and interrelationships. Results: Children at age 7 years had a higher FT3 [6.17 pmol/L, standard deviation (SD) 0.62] than children at age 15 (5.83 pmol/L, SD 0.74); P < 0.0001 with 23.2% of children at age 7 having FT3 above the adult reference range. Higher FT3 levels at age 7 in boys (P = 0.0001) and girls (P = 0.04) were associated with attainment of a more advanced pubertal stage at age 13. TSH was positively associated with FT3 at age 7 and age 15 even after adjusting for confounders. In contrast, TSH was negatively associated with FT4. Conclusions: There are substantial changes in TSH and thyroid hormone levels over childhood, in particular for FT3, which appear to relate to pubertal readiness. Our data provide increased insight into the evolution of the pituitary-thyroid axis over childhood and may have implications for determining optimal ranges for thyroid hormone replacement in children.

Cerebral salt wasting following traumatic brain injury.

SUMMARY: Hyponatraemia is the most commonly encountered electrolyte disturbance in neurological high dependency and intensive care units. Cerebral salt wasting (CSW) is the most elusive and challenging of the causes of hyponatraemia, and it is vital to distinguish it from the more familiar syndrome of inappropriate antidiuretic hormone (SIADH). Managing CSW requires correction of the intravascular volume depletion and hyponatraemia, as well as mitigation of on-going substantial sodium losses. Herein we describe a challenging case of CSW requiring large doses of hypertonic saline and the subsequent substantial benefit with the addition of fludrocortisone. LEARNING POINTS: The diagnosis of CSW requires a high index of suspicion. Distinguishing it from SIADH is essential to enable prompt treatment in order to prevent severe hyponatraemia.The hallmarks of substantial CSW are hyponatraemia, reduced volume status and inappropriately high renal sodium loss.Substantial volumes of hypertonic saline may be required for a prolonged period of time to correct volume and sodium deficits.Fludrocortisone has a role in the management of CSW. It likely reduces the doses of hypertonic saline required and can maintain serum sodium levels of hypertonic saline.

Thyroid antibody-negative euthyroid Graves' ophthalmopathy.

UNLABELLED: TSH receptor antibodies (TRAbs) are the pathological hallmark of Graves' disease, present in nearly all patients with the disease. Euthyroid Graves' ophthalmopathy (EGO) is a well-recognized clinical entity, but its occurrence in patients with negative TRAbs is a potential source of diagnostic confusion. A 66-year-old female presented to our endocrinology clinic with right eye pain and diplopia in the absence of thyroid dysfunction. TRAbs were negative, as measured with a highly sensitive third(-)generation thyrotropin-binding inhibitory immunoglobulin (TBII) ELISA assay. CT and MRI scans of the orbit showed asymmetrical thickening of the inferior rectus muscles but no other inflammatory or malignant orbital pathology. Graves' ophthalmopathy (GO) was diagnosed on the basis of the clinical and radiological features, and she underwent surgical recession of the inferior rectus muscle with complete resolution of the diplopia and orbital pain. She remained euthyroid over the course of follow-up but ultimately developed overt clinical and biochemical hyperthyroidism, 24 months after the initial presentation. By this time, she had developed positive TRAb as well as thyroid peroxidase antibodies. She responded to treatment with thionamides and remains euthyroid. This case highlights the potential for negative thyroid-specific autoantibodies in the presentation of EGO and underscores the variable temporal relationship between the clinical expression of thyroid dysfunction and orbital disease in the natural evolution of Graves' disease. LEARNING POINTS: Euthyroid Graves' ophthalmopathy can present initially with negative thyroid-specific autoantibodies.Patients with suggestive symptoms of ophthalmopathy should be carefully evaluated for GO with imaging studies even when thyroid function and autoantibodies are normal.Patients with EGO can develop thyroid dysfunction within 4 years of follow-up underpinning the need for long-term follow-up and continued patient and physician vigilance in patients who have been treated for EGO.

Weekly Intramuscular Injection of Levothyroxine following Myxoedema: A Practical Solution to an Old Crisis.

An 82-year-old female with known hypothyroidism was admitted to hospital after being found on the floor. On examination, she was unkempt, confused, bradycardic, hypothermic, and barely arousable. Initial biochemistry revealed a thyroid stimulating hormone (TSH) of >100 mU/L and free thyroxine (FT4) level of 1.5 pmol/L which supported a diagnosis of myxoedema coma. She was resuscitated and commenced on liothyronine, levothyroxine, and hydrocortisone and some improvement was made. It became apparent that she was hiding and spitting out her oral levothyroxine including levothyroxine elixir. Given the need for prompt alternative control, we sought advice from international experts where intramuscular levothyroxine was recommended. She was managed from day 50 onwards with intramuscular levothyroxine 200 mcg once a week, which was subsequently increased to 500 mcg. Thyroid function normalized and she made continual cognitive and physical progress and was discharged to a rehabilitation hospital. Her intramuscular levothyroxine was stopped and she was subsequently restarted on oral levothyroxine, with a plan for on-going close monitoring of her thyroid function. This report highlights the potential to use intramuscular levothyroxine in individuals with severe hypothyroidism arising from poor compliance with levothyroxine treatment or other potential causes such as impaired absorption.

Resistant hypertension with adrenal nodule: are we removing the right gland?

UNLABELLED: Resistant hypertension is often difficult to treat and may be associated with underlying primary aldosteronism (PA). We describe the case of an elderly gentleman who presented with severe and resistant hypertension and was found to have a left adrenal incidentaloma during evaluation but had aldosterone excess secondary to unilateral adrenal hyperplasia (UAH) of the contralateral gland, which needed surgical intervention. A 65-year-old gentleman was evaluated for uncontrolled high blood pressure (BP) in spite of taking four antihypertensive medications. The high BP was confirmed on a 24-h ambulatory reading, and further biochemical evaluation showed an elevated serum aldosterone renin ratio (ARR) (1577 pmol/l per ng per ml per h). Radiological evaluation showed an adrenal nodule (15 mm) in the left adrenal gland but an adrenal vein sampling demonstrated a lateralization towards the opposite site favouring the right adrenal to be the source of excess aldosterone. A laparoscopic right adrenalectomy was performed and the histology of the gland confirmed nodular hyperplasia. Following surgery, the patient's BP improved remarkably although he remained on antihypertensives and under regular endocrine follow-up. PA remains the most common form of secondary and difficult-to-treat hypertension. Investigations may reveal incidental adrenal lesions, which may not be the actual source of excess aldosterone, but UAH may be a contributor and may coexist and amenable to surgical treatment. An adrenal vein sampling should be undertaken for correct lateralization of the source, otherwise a correctable diagnosis may be missed and the incorrect adrenal gland may be removed. LEARNING POINTS: Severe and resistant hypertension can often be associated with underlying PA.ARR is an excellent screening tool in patients with suspected PA.Lateralization with adrenal venous sampling is essential to isolate the source and differentiate between unilateral and bilateral causes of hyperaldosteronism.Adrenal incidentalomas and UAH may coexist and the latter may often be the sole cause of excess aldosterone secretion.Decisions about adrenalectomy should be made only after integrating and interpreting radiological and biochemical test findings properly.

An atypical presentation of colonic malignancy: Clostridium septicum aortitis.

Clostridium septicum (CS) is a rare organism that accounts for only 1.3% of all clostridial infections. However, its detection is of great clinical significance, as over 80% of cases are associated with malignancy, often occult; the most common primary sites are the ascending colon and caecum, and the most common cause is haematological malignancy. We report a case of a 79-year-old woman, admitted with shortness of breath and left-sided chest pain, who, following subsequent investigations, was found to have CS aortitis. She was further evaluated with CT of the abdomen followed by colonoscopy and biopsy, which revealed adenocarcinoma of the caecum with liver metastasis. The CS aortitis has a reported mortality of 100% if left untreated. Therefore prompt intervention and surgical debridement is recommended. Despite these recommendations, our patient had some delays in her treatment and did not undergo surgical debridement due to frailty. We believe that it is highly unusual for a patient such as ours to have survived both the aortitis and the colonic malignancy, after undergoing endovascular radiological intervention and antibiotic therapy, without surgical debridement.