Progression to combined pituitary hormone deficiency common in IGHD

By Lucy Piper, Senior medwireNews Reporter

Researchers have found that a high proportion of children initially diagnosed with isolated growth hormone deficiency (IGHD) will progress to combined pituitary hormone deficiency (CPHD).

Among 83 patients, aged an average of 8.7 years and diagnosed with IGHD due to having peak GH levels being below 5 μg/L during hypoglycaemia and clonidine stimulation, 37 (44.6%) developed CPHD over an average follow-up of 15 years in a single tertiary referral centre.

Commenting on the findings for medwireNews, Professor Martin Savage, from Barts and the London School of Medicine & Dentistry in London, UK, pointed out the severity of GHD in these patients, all of whom had a peak GH below 3.8 μg/L.

“These findings put such patients in a different category of endocrine disorders compared to patients with mild GHD, ie, peak GH 5 to10 μg/L”, he said.

“Patients with mild GHD do not usually develop pituitary hormone deficiencies and generally have normal GH responses to stimulation when they are re-tested at completion of linear growth. Consequently, subjects with severe IGHD need careful long-term endocrine follow-up.”

The study researchers Alexander Jorge (Universidade de Sao Paulo, Brazil) and colleagues also note that progression to CPHD occurred after a median of 5.4 years in half of the patients, reinforcing “the need for lifelong monitoring of pituitary function in IGHD patients”, they say. Indeed, they found that, for some individuals, progression to a second pituitary hormone deficiency occurred up to 21.2 years after GHD diagnosis.

Luteinising hormone (LH) and follicle-stimulating hormone (FSH) were the most common pituitary hormone deficiencies to develop, affecting 38% of patients, followed by thyroid-stimulating hormone (TSH; 31%), adrenocorticotropic hormone (ACTH; 12%) and antidiuretic hormone (ADH; 5%) deficiencies.

Savage noted that such deficiencies are “treatable with appropriate replacements, but if undetected can lead to significantly impaired quality of life.”

TSH and LH/FSH deficiencies developed an average of 7.5 and 8.3 years after GHD diagnosis, respectively, while ADH deficiency developed earlier, at an average of 3.1 years, and ACTH deficiency later, at an average of 9.3 years.

The strongest predictor for CPHD development was pituitary stalk abnormality, demonstrated by magnetic resonance imaging (MRI) at the time of IGHD diagnosis, which increased the risk of progression 3.28-fold, the researchers report in Pituitary.

Among the 44 (53%) children with this abnormality at initial diagnosis, 27 (73%) developed a second hormone deficiency. By contrast, only two of 16 patients with normal MRI scans at initial diagnosis developed CPHD, one of whom had a heterozygous autosomal dominant GH1 splice site mutation known to evolve with other pituitary hormone deficiencies, the team comments.

This “emphasises the importance of pituitary MRI scanning at the time of initial diagnosis and particularly confirms the importance of quality reporting of the MRI findings”, Savage pointed out.

“MRI abnormalities such as pituitary stalk defects, pituitary hypoplasia and ectopic posterior pituitary are key findings which increase the likelihood of subsequent additional hormonal deficiencies. Such patients require close specialist follow-up.”

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