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M. A. B. Naafs, H. R. A. Fischer, P.C. van der Velden, H. Mulder, W. H. L. Hackeng, W. Schopman, G. Koorevaar and J. Silberbusch

Abstract. Ten hypercalcaemic patients with solid tumours were studied to evaluate the renal response on PTH infusion as assessed by nephrogenous cAMP excretion and maximum tubular re-absorption of phosphate. In addition, 20 normocalcaemic patients, 11 with an adenocarcinoma and 9 with a squamous cell carcinoma, were studied. All cancer patients had moderately extensive disease. Results were compared with those of 9 patients with primary hyperparathyroidism and with 10 elderly controls. All groups studied had comparable renal function, magnesium and 25-hydroxy-vitamin D levels. Comparable results were obtained in patients with an adenocarcinoma and in controls. cAMP response (Δ nephrogenous cAMP) was significantly lower in the hypercalcaemic patients with a solid tumour compared with the controls (8.13 ± 4.68 nmol/100 ml glomerular filtrate vs 29.52 ± 25.62 nmol/100 ml glomerular filtrate; P < 0.005). In the group of patients with primary hyperparathyroidism Δ nephrogenous cAMP was 13.41 ± 7.54 nmol/100 ml glomerular filtrate (P < 0.06 vs controls). The group of patients with a squamous cell cancer showed an intermediate value of 14.83 ± 10.74 nmol/100 ml glomerular filtrate (P < 0.025 vs the normocalcaemic adenocarcinoma patients, but NS vs controls). In two hypercalcaemic patients with a solid tumour in whom PTH infusion was repeated after normalization of serum calcium no influence on renal responsiveness was observed. Responses of maximum tubular re-absorption of phosphate were lowest in the group of hypercalcaemic patients with a solid tumour and in the patients with primary hyperparathyroidism compared with controls (0.11 ± 0.10 vs 0.22 ± 0.09 mmol/l and 0.09 ± vs 0.22 ± 0.09 mmol/l; P <0.025 and P <0.005, respectively). It is concluded that in hypercalcaemic patients with a solid tumour a humoral factor is present which inhibits the interaction of exogenous PTH and its renal receptors. In a subset of normocalcaemic patients with a squamous cell cancer the same circulating factor might be present.

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M. A. B. Naafs, P. C. van der Velden, H. R. A. Fischer, G. Koorevaar, S. van Duin, W. H. L. Hackeng, W. Schopman and J. Silberbusch

Abstract. Plasma cyclic AMP (PcAMP) concentration and the excretion of cyclic AMP dl GF were estimated in 11 thyrotoxic patients before and after medical treatment.

PcAMP concentrations were significantly higher during hyperthyroidism (2.30 ± 0.69 vs 1.88 ± 0.71 nmoldl; P < 0.05), and total urinary cyclic AMP (TcAMP) excretion showed no significant changes (3.24 ± 0.64 vs 3.44 ± 1.77 nmol/dl GF). Nephrogenous (NcAMP) excretion rose significantly (1.00 ±0.82 vs 1.68 ±1.31 mmol/dl GF; P < 0.025). The increase in NcAMP excretion correlated significantly with the decrease in serum T3 levels (r = -0.46; P < 0.05). Serum iPTH levels showed no significant change. Both the serum Ca, corrected for serum total protein and TmPO4 GFR declined after treatment (respectively 2.44 ± 0.13 vs 2.33 ± 0.08 mmol l; P <0.05 and 1.18 ± 0.29 vs 1.05 ±0.22 mmol/l; P < 0.05). It is concluded that the rise in NcAMP excretion corroborates the concept of increasing parathyroid activity following the treatment of hyperthyroidism.

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J C Naafs, L M Vendrig, J Limpens, H J van der Lee, R G Duijnhoven, J P Marchal, A S van Trotsenburg and N Zwaveling-Soonawala

Objective

To provide an overview of cognitive and motor outcome, and quality of life (QoL) in patients with congenital central hypothyroidism (CH-C).

Design

Systematic review with individual patient data (IPD) meta-analysis.

Methods

OVID MEDLINE, EMBASE and PsycInfo were searched from inception to June 11th, 2019. Studies in patients with CH-C, either isolated or with multiple pituitary hormone deficiency (MPHD), were included if CH-C patients could be separated from any additional patient groups. Primary outcomes were full-scale intelligence quotient (FSIQ) and motor outcome; secondary outcome was QoL. Following data-extraction, one-stage IPD meta-analysis was performed, fitting a linear mixed model with FSIQ as dependent variable. Random intercepts were fitted for each study.

Results

Six studies measuring FSIQ were eligible for meta-analysis, comprising 30 CH-C patients (20 males; 27 MPHD patients). FSIQ range was wide (64–123). Mean weighted FSIQ was 97 (95% CI: 88–105). Twenty-seven percent had an FSIQ below 85 (≥1 s.d. below norm score), and 10% below 70 (≥2 s.d. below norm score). There was no significant association between FSIQ and sex or age. Age at treatment initiation was available from three studies only, thus impeding a reliable analysis of this parameter. Motor outcome and QoL were each studied in one study; no quantitative analyses could be performed for these outcomes.

Conclusion

A wide range in FSIQ scores was observed in CH-C patients. Results should be interpreted with caution, because included patients mainly had MPHD and age at treatment initiation was unknown for the majority of patients.