Probable Hypopituitarism in an Infant


Question

I need your help in managing one of my patients.

It was an interesting set up: FT NB baby boy had somewhat complicated delivery, few self -resolved hypoglycemias and was kind of too sleepy/ uninterested in feeding for about 10 days -longer then looked appropriate for the degree of his birth stress, so brain MRI was done. Ectopic small pituitary gland with no visualized pituitary stalk and partial absence of anterior falx were seen. Initial labs at age of 2 weeks showed TSH-5.6, T4 -QNS, LH/FSH <0.2, prolactin 30.1, IGF-1<25, bili 9.2/0.9 (high for 2 weeks), cortisol 1.3.

I was concerned about low cortisol, so ACTH test was done. The samples for 0 and 60' were combined by lab(!!!), so there was no repeat cortisol level at all.I could not r/out panhypopit as well as confirm it for sure, so, as soon as baby was doing better and had no hypoglycemias, he was d/c home with teaching about emergency Solu-Cortef injection and F/up.Meanwhile, abnormal NB screen with low TT4 and normal TSH came, suggestive of central hypothyroidism. R epeat TFT at 3 weeks of age again did not have thyroxin (QNS), and TSH was normal -4.6 .

Repeat TFT's showed low FT4 of 0.65 (No TSH in this set because of inability to get enough blood, previous TSH of 4.6 was 3 days ago) Also we found very low Testosterone-7.3, IGF-1 of 17 (mean 55, range 15-109), IGF-BP-3 -1.1 (range 0.7-3.6)

I started this baby on Levoxyl 25 mcg, thinking of possible central hypothyroidism in the light of previous events/findings. Baby was close to 4 weeks old and still had some mild jaundice, supporting my concerns about hypothyroidism.I saw the baby at age of 7 weeks (in 3 weeks after starting Levoxyl) and found well looking active infant boy growing at 90% for Wt and Ht, gaining 700gm (wt-5.4kg) and 4 cm (L-60cm) I repeated TFT's in 3 weeks after starting on Levoxyl 25 mcg: TSH-0.015, FT4-1.69 (0.76-2.00). I wanted the repeat Testosterone to assess the minipuberty, but it was QNS again.

I contacted the mother and while discussing the results, figured out that she thinks that the baby is eating too much and is kind of too active.I decreased the dose to 12.5 mcg, mentioned to her that we will check the levels in 2 weeks. Also I mentioned that I would ask your opinion.

Now are my questions about thyroid aspect of this difficult patient:

Is this an iatrogenic suppression of TSH by too high Levoxyl dose(although it is 5mcg/kg only)? I tend to think so, because we had 3 previous normal levels of TSH before treatment.Or this is a declined function of the thyreotrops of the displaced pituitary?Have no answer for this, as soon as low IGF, low T are suggestive of loss of function. But clinically baby is doing and growing fine, so no data for growth failure and GH deficiency though.

What is my next action if TSH is still suppressed/low and FT4 is still in the high normal? Ignore it or d/c Levoxyl completely?

Does it look like central CH? I would value you opinions and suggestions a lot.I will inform you about future tests and events if you are interested.Thank you so much in advance. Irina Kazachkova, MD, Maimonides Medical Center,

Response

I think that your patient almost certainly is GH, ACTH and TSH ( and probably LH/FSH) deficient- based on the exceedingly low IGF-1, and low free T4 and random cortisol values. As you know babies with GH (and ACTH) deficiency are at risk of hypoglycemia, but often the blood glucose is only low after fasting, so the fact that you have not documented it does not necessarily rule it out. You need to check a blood sugar prior to the next feed, and be particularly concerned as the baby sleeps longer and longer during the night.

In my opinion, this baby should be started on GH, and cortisol (in addition to T4) ASAP. If it is that difficult to obtain blood and you cannot do either a GH stimulation test (arginine/glucagon) or ACTH test, I would just treat speculatively. Note that with a glucagon stimulation test you can also assess cortisol. With the evidence you have, there is not too much doubt about the dx and many insurance companies will not require formal stimulation tests. I would use a low cortisol replacement dose (<10 mg/kg/day) because of the growth-suppressive effect of cortisol. I would probably use 0.15-2 mg/kg/wk of GH given daily and titrate the dose thereafter according to the growth response, although initially one treats because of the adverse metabolic consequences rather than the growth effects of GH deficiency.

As far as the suppressed TSH is concerned, if the baby is TSH deficient then the TSH is not very helpful in monitoring the adequacy of thyroid hormone replacement and I would follow the free T4. I would not reduce the L-T4 dose (unless the free T4 is elevated using age-appropriate norms).Sincerely, Rosalind S. Brown, M.D.,