Management of Glucocorticoid Replacement in Adult Growth Hormone Deficiency

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Context: The diagnosis of central hypothyroidism (CH) is often difficult to establish as serum TSH levels may be low, normal, or slightly increased. Objective: To explore the use of recombinant human TSH (rhTSH) in the diagnosis of CH. Design: Randomized single-blind clinical trial. Setting: Outpatient clinic of a tertiary care referral center. Intervention: A single intramuscular injection of 0.1 and 0.9 mg rhTSH in random order with 1-week interval. Participants: Eighteen adult patients with pituitary insufficiency and six healthy age-, sex-, and body mass index-matched controls. Six patients had untreated CH (newCH), six had treated CH (CH), and six patients were TSH sufficient (nonCH). Five weeks before TSH stimulation, levothyroxine was replaced with tri-iodothyronine (T 3 ) for 4 weeks. One week before stimulation, treatment was withdrawn. Main outcome measures: Thyroid hormones and thyroglobulin (Tg) before and 2, 3 1 ⁄ 2 , 7, 24, 48, and 72 h after each injection. Results: In the newCH group, basal free thyroxine (FT 4 ) levels were lower than in controls (P!0.05). After 0.9 mg rhTSH, the increases in FT 4 and reverse T 3 (rT 3 ) were less marked in the newCH group than in controls (FT 4 GS.E.M. 9.2G0.5 to 19.7G1.2 vs 11.3G0.5 to 27.8.2G2.4 pmol/l, P!0.05). The CH group exhibited reduced basal and stimulated FT 4 compared with the TSH-sufficient groups. Tg increased similarly among all study groups after rhTSH injection. Conclusion: In this pilot study, patients with untreated CH had lower response to 0.9 mg rhTSH in FT 4 and rT 3 than controls. An rhTSH test may be useful in the diagnosis of CH, but further studies are required.European Journal of Endocrinology 159 153-160

Section: Discussionmentioning

confidence: 99%

Exploring the use of recombinant human TSH in the diagnosis of central hypothyroidism

Filipsson¹,

Nyström²,

Johannsson³

2008

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GH replacement in adults: interactions with other pituitary hormone deficiencies and replacement therapies

Filipsson

Johannsson

2009

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Severe GH deficiency (GHD) in adults has been described as a clinical entity. However, some of the features associated with GHD could be due to unphysiological and inadequate replacement of other pituitary hormone deficiencies. This may be true for glucocorticoid replacement that lacks a biomarker making dose titration and monitoring difficult. Moreover, oral estrogen replacement therapy decreases IGF1 levels compared with the transdermal route, which attenuates the responsiveness to GH replacement therapy in women. In addition, in untreated female hypogonadism, oral estrogen may augment the features associated with GHD in adult women. Important interactions between the hormones used for replacing pituitary hormone deficiency occur. Introducing GH replacement may unmask both an incipient adrenal insufficiency and central hypothyroidism. Therefore, awareness and proper monitoring of these hormonal interactions are important in order to reach an optimal replacement therapy. This review will focus on the complex hormonal interactions between GH and other pituitary hormones in GHD and in GH replacement. European Journal of Endocrinology 161 S85-S95

THERAPY OF ENDOCRINE DISEASE: Perspectives on the management of adrenal insufficiency: clinical insights from across Europe

Grossman

Johannsson

Quinkler

et al. 2013

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108

109

BackgroundConventional glucocorticoid (GC) replacement for patients with adrenal insufficiency (AI) is inadequate. Patients with AI continue to have increased mortality and morbidity and compromised quality of life despite treatment and monitoring.Objectivesi) To review current management of AI and the unmet medical need based on literature and treatment experience and ii) to offer practical advice for managing AI in specific clinical situations.MethodsThe review considers the most urgent questions endocrinologists face in managing AI and presents generalised patient cases with suggested strategies for treatment.ResultsOptimisation and individualisation of GC replacement remain a challenge because available therapies do not mimic physiological cortisol patterns. While increased mortality and morbidity appear related to inadequate GC replacement, there are no objective measures to guide dose selection and optimisation. Physicians must rely on experience to recognise the clinical signs, which are not unique to AI, of inadequate treatment. The increased demand for corticosteroids during periods of stress can result in a life-threatening adrenal crisis (AC) in a patient with AI. Education is paramount for patients and their caregivers to anticipate, recognise and provide proper early treatment to prevent or reduce the occurrence of ACs.ConclusionsThis review highlights and offers suggestions to address the challenges endocrinologists encounter in treating patients with AI. New preparations are being developed to better mimic normal physiological cortisol levels with convenient, once-daily dosing which may improve treatment outcomes.