Diagnosis and treatment of hypothyroidism in TSH deficiency compared to primary thyroid disease: pituitary patients are at risk of under-replacement with levothyroxine

Koulouri, Olympia; Auldin, Mohammed A.; Agarwal, Ravi; Kieffer, Veronica; Robertson, Carole; Smith, James Falconer; Levy, Miles; Howlett, Trevor A.

doi:10.1111/j.1365-2265.2011.03984.x

Cited by 68 publications

(45 citation statements)

References 6 publications

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“…The determination of circulating free thyroid hormone levels is of major significance in monitoring L-T4 treatment in CeH patients (Ferretti et al, 1999;Alexopoulou et al, 2004;Slawik et al, 2007;Iverson and Mariash, 2008;Koulouri et al, 2011;Beck-Peccoz, 2011;Persani, 2012). If blood is withdrawn before the morning administration of L-T4, low free T 4 values may suggest undertreatment and high free T 3 values are more sensitive for disclosing overtreatment.…”

Section: Facts and Uncertainties In Central Hypothyroidism Replacemenmentioning

confidence: 99%

“…Very recently, Koulouri et al (2011) compared free T 4 values in a large series of patients with hypothalamicpituitary lesions with those of patients with primary thyroid disease adequately treated with L-T4, i.e., those with normal levels of circulating TSH during replacement therapy. The conclusions were that CeH patients The diamonds indicate mean (AEstandard deviation).…”

Section: Facts and Uncertainties In Central Hypothyroidism Replacemenmentioning

confidence: 99%

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Uncertainties in endocrine substitution therapy for central endocrine insufficiencies

Persani

Bonomi

2014

Clinical Neuroendocrinology

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Section: Facts and Uncertainties In Central Hypothyroidism Replacemenmentioning

confidence: 99%

Section: Facts and Uncertainties In Central Hypothyroidism Replacemenmentioning

confidence: 99%

Uncertainties in endocrine substitution therapy for central endocrine insufficiencies

Persani

Bonomi

2014

Clinical Neuroendocrinology

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“…The determination of FT4 acquires a more relevant role in the evaluation of replacement therapy than in primary hypothyroidism. Several groups [49,56,58,60] reported that concentrations of FT4 in the upper part of normal range might represent an appropriate target in most treated CeH patients (Recommendation 26).…”

Section: How Should Ceh Patients Be Managed and Treated?mentioning

confidence: 99%

“…The determination of circulating free thyroid hormone concentrations is of major significance in monitoring L-T4 treatment in CeH patients [1,24,25,49,[56][57][58]. Blood should be withdrawn before or at least 4 h after the L-T4 administration [59].…”

Section: How Should Ceh Patients Be Managed and Treated?mentioning

confidence: 99%

2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism

Persani¹,

Brabant

Dattani³

et al. 2018

Eur Thyroid J

159

145

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Objectives: Central hypothyroidism (CeH) is a rare form of hypothyroidism characterized by insufficient thyroid stimulation due to disturbed pituitary and/or hypothalamic functioning. Due to its origin and the whole clinical context, CeH represents a challenging condition in clinical practice as it is characterized by suboptimal accuracy of clinical and biochemical parameters for diagnosis and management. Since no expert consensus or guidance for this condition is currently available, a task force of experts received the commitment from the European Thyroid Association (ETA) to prepare this document based on the principles of clinical evidence. Study Design: The task force started to work in February 2017 and after a careful selection of appropriate references (cohort studies, case reports, expert opinions), a preliminary presentation and live discussion during the 2017 ETA meeting, and several revision rounds, has prepared a list of recommendations to support the diagnosis and management of patients with CeH. Results: Due to the particular challenges of this rare condition in the different ages, the target users of this guidance are pediatric and adult endocrinologists. Experts agreed on the need to recognize and treat overt CeH at all ages, whereas treatment of milder forms may be dispensable in the elderly (> 75 years). Conclusions: Despite the lack of randomized controlled clinical trials, the experts provide 34 recommendations supported by variable levels of strength that should improve the quality of life of the affected patients and reduce the metabolic and hormonal consequences of inadequate management.

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“…In recent years, several papers dealing with substitutive LT4 therapy in patients with CH have been published and all have underlined the pitfalls in achieving optimal replacement because the inability to be guided by serum TSH levels. [8][9][10] The article of Koulouri et al 11 in this issue of Clinical Endocrinology approaches the topic in a new and interesting way. They used their Depatment's clinical information system to identify all patients with hypothalamo-pituitary lesions and divided them into high risk and low risk of CH.…”

mentioning

confidence: 99%

Treatment of central hypothyroidism*

Beck‐Peccoz

2011

Clinical Endocrinology

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Central hypothyroidism (CH) is a rare cause of hypothyroidism. 1,2 Its prevalence in the general population is estimated to be around 1:80 000-1:120 000 individuals. About 1 out of 30-40 newborns with congenital hypothyroidism is affected with CH. CH is the consequence of insufficient stimulation of an otherwise normal thyroid gland and is caused by either pituitary (secondary hypothyroidism) or hypothalamic (tertiary hypothyroidism) defects due to neoplastic lesions, infective and inflammatory diseases, autoimmunity, traumatic brain injury, etc. Secondary hypothyroidism usually implies a reduction in the number of functioning thyrotrophs, as documented by impaired TSH secretion and by the blunted response of TSH to TRH. Tertiary hypothyroidism is characterized by normal or slightly elevated serum concentrations of immunoreactive TSH and qualitative abnormalities of TSH secretion, such as decreased bioactivity of circulating molecules, lack of nocturnal TSH surge, and delayed and/or exaggerated and prolonged TSH response to TRH.1 The genetic forms of CH can be isolated, if the defect is limited to thyrotroph function (isolated TSH deficiency), or associated with combined pituitary hormone deficiency (CPHD), if the defect involves other pituitary cell lineages. 3 In the case of isolated TSH deficiency, mutations in thyrotroph-specific genes, such as TSHb or TRH-Receptor (TRH-R), have been demonstrated. In the case of CPHDs, various genes encoding transcription factors required for correct development and/or function of several pituitary cell lineages, such as HESX1, LHX 3, LHX 4, SOX 3 and PROP1, may be involved. Although most of the aetiopathological mechanisms of CH have been recognized, both the diagnosis and the treatment of CH can still be difficult. In fact, the clinical picture of many patients with CH is mild and the onset can be progressive. The clinical consequences of CH in both children and adults may vary greatly depending on the aetiology, the severity of thyroid impairment, the extent of any associated hormone deficiencies, and the age of the patient at the time of the onset of the disease. In general, acquired CH is less severe than the congenital form because some thyroid hormone secretion is assured by constitutive activity of the TSH receptor.4 Symptoms and signs of thyroid insufficiency are usually milder than those of primary hypothyroidism and goitre is always absent. 2 In the case of CPHD, most patients have other endocrine manifestations of the disease (growth failure, delayed puberty, adrenal insufficiency, diabetes insipidus) that lead them to seek medical attention before their hypothyroidism becomes severe. Early diagnosis of the congenital form by neonatal screening for hypothyroidism, based on both T4 and TSH measurement, is strongly recommended in order to avoid possible development of cretinism. 5Due to the difficulties in recognizing CH on clinical grounds, the diagnosis is usually made on a biochemical basis. The measurement of circulating free thyroxine with direct 'two-step' me...

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Diagnosis and treatment of hypothyroidism in TSH deficiency compared to primary thyroid disease: pituitary patients are at risk of under-replacement with levothyroxine

Cited by 68 publications

References 6 publications

Uncertainties in endocrine substitution therapy for central endocrine insufficiencies

Uncertainties in endocrine substitution therapy for central endocrine insufficiencies

2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism

Treatment of central hypothyroidism*

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